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Mosiej W, Długosz E, Kruk M, Zielińska D. Immunomodulatory Properties of Live and Thermally-Inactivated Food-Origin Lactic Acid Bacteria-In Vitro Studies. Mol Nutr Food Res 2025:e70047. [PMID: 40166824 DOI: 10.1002/mnfr.70047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 03/03/2025] [Accepted: 03/10/2025] [Indexed: 04/02/2025]
Abstract
The study investigates the strain-specific immunomodulatory properties of live and thermally-inactivated (TI) lactic acid bacteria (LAB) derived from traditional Polish fermented foods, focusing on their potential as probiotics and postbiotics. LAB strains, known for their role in food fermentation, were assessed for their ability to influence cytokine production in THP-1 macrophages, maintain intestinal epithelial barrier integrity in Caco-2 monolayers, exhibit antioxidant activity, and produce specific organic acids and sugars. The research demonstrated that live LAB strains significantly upregulated the anti-inflammatory cytokine IL-10, particularly under inflammatory conditions, while TI strains exhibited notable antioxidant and anti-inflammatory properties. TI strains showed a greater ability to protect epithelial barrier function and reduce pro-inflammatory cytokine secretion than live strains, suggesting a promising role for postbiotics. The findings underscore the potential of LAB from fermented foods, demonstrating that postbiotic derivatives can differently influence inflammation compared to live bacteria, highlighting their potential as immune-enhancing agents, capable of modulating immune responses and offering therapeutic benefits against inflammation-related disorders. However, the limitations of in vitro models highlight the need for further in vivo and clinical studies to validate these effects and fully uncover the health benefits of these LAB strains for humans.
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Affiliation(s)
- Wioletta Mosiej
- Department of Food Gastronomy and Food Hygiene, Institute of Human Nutrition Sciences, Warsaw University of Life Science - SGGW, Warsaw, Poland
| | - Ewa Długosz
- Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Science - SGGW, Warsaw, Poland
| | - Marcin Kruk
- Department of Food Gastronomy and Food Hygiene, Institute of Human Nutrition Sciences, Warsaw University of Life Science - SGGW, Warsaw, Poland
| | - Dorota Zielińska
- Department of Food Gastronomy and Food Hygiene, Institute of Human Nutrition Sciences, Warsaw University of Life Science - SGGW, Warsaw, Poland
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Zhao Z, Han L, Tuerxunbieke B, Ming L, Ji J, Chen Y, Sun R, Tian W, Yang F, Huang Q. Effects of gut microbiota and metabolites on pancreatitis: a 2-sample Mendelian randomization study. J Gastrointest Surg 2025; 29:101885. [PMID: 39549891 DOI: 10.1016/j.gassur.2024.101885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/29/2024] [Accepted: 11/08/2024] [Indexed: 11/18/2024]
Abstract
BACKGROUND Acute pancreatitis (AP) and chronic pancreatitis (CP) have high incidences and poor prognoses. The early screening of at-risk populations still awaits further study. The limitation was mainly based on observational studies, with limited sample size and the presence of confounding factors. This study used a 2-sample Mendelian randomization (MR) analysis based on publicly available data from genome-wide association studies to reveal the causal effect of gut microbiota and metabolites on pancreatitis. METHODS This study collected summary statistics on gut microbiota, metabolites, AP, and CP. A 2-sample MR analysis was performed using MR-Egger, inverse variance-weighted, MR Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median. RESULTS The 2-sample MR showed that only Eubacterium coprostanoligenes was an independent protective factor for AP among all gut microbiota, and the other microbiota were not significant for pancreatitis. Unsaturated fatty acids in metabolites are protective factors for both AP (odds ratio [OR], 0.730; 95% CI, 0.593-0.899; P = .003) and CP (OR, 0.660; 95% CI, 0.457-0.916; P = .013). Furthermore, carnitine was a protective factor CP, and glucose was an independent risk factor for CP. CONCLUSION This study provides potential evidence of the causal role of gut microbiota and metabolites on pancreatitis, which may be conducive for designing microbiome and metabolite interventions on AP or CP in the future.
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Affiliation(s)
- Zhirong Zhao
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Li Han
- Ultrasound Medical Center, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Baobaonai Tuerxunbieke
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Lan Ming
- Yancheng Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, China; Yancheng Traditional Chinese Medicine Hospital, Yancheng, Jiangsu Province, China
| | - Jiamin Ji
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yuan Chen
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Ran Sun
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Weiliang Tian
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Fan Yang
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Qian Huang
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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Liu Q, Ruan K, An Z, Li L, Ding C, Xu D, Yang J, Zhang X. Updated review of research on the role of the gut microbiota and microbiota-derived metabolites in acute pancreatitis progression and inflammation-targeted therapy. Int J Biol Sci 2025; 21:1242-1258. [PMID: 39897025 PMCID: PMC11781165 DOI: 10.7150/ijbs.108858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 01/10/2025] [Indexed: 02/04/2025] Open
Abstract
Acute pancreatitis (AP) is characterized by autodigestion of the pancreas, and some patients may rapidly progress to systemic inflammation, pancreatic necrosis, and multi-organ failure. Numerous studies have detailed the bidirectional communication networks between the pancreas and the intestinal microbiota, as well as its metabolites. Such crosstalk affects the progression of AP and recovery through intestinal barrier disruption. Furthermore, advances in experimental research and clinical studies have indicated that gut microorganisms exhibit distinct alterations in response to different levels of severity and etiologies of AP. This information has greatly expanded our knowledge of the role of the gut microflora and microbial metabolites in the pathology of disease and has reinforced the basis of therapeutic approaches that target candidate intestinal microbiota. In this review, we aim to provide an overview of the composition and diversity of the gut microbial community, to highlight the candidate bacteria and microbiota-derived metabolites responsible for AP, and to elucidate their interactions with and regulation of immune-relevant receptors in intestinal epithelial cells (IECs) in the host. Future research should focus on identifying and characterizing AP-associated bacterial strains, elucidating their distinct pathogenic mechanisms across different etiologies and stages of AP, and leveraging these insights to develop preventive and therapeutic strategies.
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Affiliation(s)
- Qiang Liu
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310058, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, Hangzhou 310006, China
| | - Kaiyi Ruan
- Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Zihui An
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, Hangzhou 310006, China
| | - Lingyun Li
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, Hangzhou 310006, China
| | - Cong Ding
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310058, China
| | - Dongchao Xu
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, Hangzhou 310006, China
| | - Jianfeng Yang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310058, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, Hangzhou 310006, China
| | - Xiaofeng Zhang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310058, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, Hangzhou 310006, China
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Gu R, Wei H, Cui T, Wang G, Luan Y, Liu R, Yin C. Angiotensin-(1-7) improves intestinal microbiota disturbances and modulates fecal metabolic aberrations in acute pancreatitis. FASEB J 2024; 38:e70134. [PMID: 39453737 DOI: 10.1096/fj.202401565rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 10/07/2024] [Accepted: 10/15/2024] [Indexed: 10/27/2024]
Abstract
Acute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang-(1-7) on AP-induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang-(1-7) via tail vein injection, and AP + Ang-(1-7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang-(1-7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang-(1-7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang-(1-7) reversing AP-induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang-(1-7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.
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Affiliation(s)
- Ruru Gu
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
- Department of Gastroenterology, the Second Hospital of Shandong University, Jinan, China
| | - Hongtao Wei
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Tianyu Cui
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
| | - Guoxing Wang
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yingyi Luan
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
| | - Ruixia Liu
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
| | - Chenghong Yin
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
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Gong L, Zhao S, Liang B, Wei S, Zhang Y, Li S, Yang H, Jiang P. Systematic metabolic profiling of mice with caerulein-induced acute pancreatitis. Transl Gastroenterol Hepatol 2024; 9:65. [PMID: 39503020 PMCID: PMC11535808 DOI: 10.21037/tgh-24-14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 06/24/2024] [Indexed: 11/08/2024] Open
Abstract
Background Acute pancreatitis (AP) is a complex inflammatory condition with rising incidence globally. Despite various known causes, early diagnosis remains challenging due to limitations in existing biomarkers. Metabolomics offers a promising avenue for identifying novel biomarkers and elucidating underlying pathophysiological mechanisms. Previous AP metabolomics studies primarily focused on analyzing serum, urine, and pancreatic tissues from patients or animal models. However, systematic metabolomics studies that analyze multiple tissues simultaneously are still lacking. The primary aim of our study is to obtain valuable clues to explore the pathophysiological mechanisms of AP and discover novel biomarkers to enable early detection. Methods Using a mouse model of AP induced by cerulein, we conducted gas chromatography-mass spectrometry (GC-MS) metabolomic analysis on serum, pancreas, liver, spleen, colon, and kidney samples. Twelve male C57BL/6J mice were randomly divided into AP and control (CON) groups. Serum and tissue samples were collected, processed, and analyzed using established protocols. Multivariate statistical analysis was employed to identify differential metabolites and impacted metabolic pathways. Results Distinct metabolic profiles were observed between AP and CON groups across multiple tissues. Elevated levels of ketone bodies, amino acids, citric acid, and lipids were noted, with significant differences in metabolite levels identified. Notably, 3-hydroxybutyric acid (3-HBA), branched-chain amino acids (BCAAs), phenylalanine, and L-lysine showed consistent alterations, suggesting their potential as early diagnostic biomarkers for AP. Pathway analysis revealed perturbations in several metabolic pathways, providing insights into the pathophysiological mechanisms underlying AP. Conclusions Our study highlights the utility of metabolomics in identifying potential biomarkers for early diagnosis of AP and elucidating associated metabolic pathways. 3-HBA, BCAAs, phenylalanine and L-lysine emerge as promising biomarkers for further clinical validation. These findings contribute to a better understanding of AP pathophysiology and underscore the potential of metabolomics in precision medicine approaches for AP management.
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Affiliation(s)
- Linqiang Gong
- Department of Gastroenterology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Shiyuan Zhao
- Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, China
- Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, China
| | - Benhui Liang
- Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Shanshan Wei
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Graduate Department, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China
| | - Yazhou Zhang
- Department of Foot and Ankle Surgery, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Shuhui Li
- Department of Gastroenterology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Hui Yang
- Department of Gynecology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Pei Jiang
- Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, China
- Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, China
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Li Y, Li J, Li S, Zhou S, Yang J, Xu K, Chen Y. Exploring the gut microbiota's crucial role in acute pancreatitis and the novel therapeutic potential of derived extracellular vesicles. Front Pharmacol 2024; 15:1437894. [PMID: 39130638 PMCID: PMC11310017 DOI: 10.3389/fphar.2024.1437894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 07/15/2024] [Indexed: 08/13/2024] Open
Abstract
During acute pancreatitis, intestinal permeability increases due to intestinal motility dysfunction, microcirculatory disorders, and ischemia-reperfusion injury, and disturbances in the intestinal flora make bacterial translocation easier, which consequently leads to local or systemic complications such as pancreatic and peripancreatic necrotic infections, acute lung injury, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Therefore, adjusting intestinal ecosystem balance may be a promising approach to control local and systemic complications of acute pancreatitis. In this paper, we reviewed the causes and manifestations of intestinal flora disorders during acute pancreatitis and their complications, focused on the reduction of acute pancreatitis and its complications by adjusting the intestinal microbial balance, and innovatively proposed the treatment of acute pancreatitis and its complications by gut microbiota-derived extracellular vesicles.
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Affiliation(s)
- Yijie Li
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jie Li
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Sen Li
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shumin Zhou
- Wenzhou Institute of Shanghai University, Wenzhou, China
| | - Jiahua Yang
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ke Xu
- Wenzhou Institute of Shanghai University, Wenzhou, China
- Institute of Translational Medicine, Shanghai University, Shanghai, China
| | - Yafeng Chen
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Thompson RS, Bowers SJ, Vargas F, Hopkins S, Kelley T, Gonzalez A, Lowry CA, Dorrestein PC, Vitaterna MH, Turek FW, Knight R, Wright KP, Fleshner M. A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats. Nutrients 2024; 16:1790. [PMID: 38892722 PMCID: PMC11175065 DOI: 10.3390/nu16111790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 05/30/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024] Open
Abstract
Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbially modified metabolites over time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides (GOS) and polydextrose (PDX)), compared to a control diet, would consistently impact the gut microbiome and microbially modified bile acids over time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiomes and metabolomes were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered the beta diversity, relative abundance of bacterial genera, and microbially modified bile acids over time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by the prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbially modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites, supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.
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Affiliation(s)
- Robert S. Thompson
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Samuel J. Bowers
- Department of Neurobiology, Northwestern University, Center for Sleep and Circadian Biology, Evanston, IL 60208, USA; (S.J.B.); (M.H.V.); (F.W.T.)
| | - Fernando Vargas
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA 92093, USA (P.C.D.)
| | - Shelby Hopkins
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Tel Kelley
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
| | - Antonio Gonzalez
- Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA (R.K.)
| | - Christopher A. Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Pieter C. Dorrestein
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA 92093, USA (P.C.D.)
| | - Martha Hotz Vitaterna
- Department of Neurobiology, Northwestern University, Center for Sleep and Circadian Biology, Evanston, IL 60208, USA; (S.J.B.); (M.H.V.); (F.W.T.)
| | - Fred W. Turek
- Department of Neurobiology, Northwestern University, Center for Sleep and Circadian Biology, Evanston, IL 60208, USA; (S.J.B.); (M.H.V.); (F.W.T.)
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA (R.K.)
- Department of Computer Science and Engineering, University of California San Diego, San Diego, CA 92093, USA
- Center for Microbiome Innovation, University of California San Diego, San Diego, CA 92093, USA
| | - Kenneth P. Wright
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Monika Fleshner
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; (R.S.T.); (T.K.); (C.A.L.); (K.P.W.J.)
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA
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He L, Luo H, Li Y, Zhang Y, Peng L, Xu Y, Lu J, Li J, Liu H. The causal relationship between the gut microbiota and acute pancreatitis: A 2-sample Mendelian randomization study. Medicine (Baltimore) 2024; 103:e38331. [PMID: 39259083 PMCID: PMC11142829 DOI: 10.1097/md.0000000000038331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/05/2024] [Accepted: 05/02/2024] [Indexed: 09/12/2024] Open
Abstract
Several observational studies have reported a correlation between the gut microbiota (GM) and the risk of acute pancreatitis (AP). However, the causal relationship between them remains uncertain. We conducted a 2-sample Mendelian randomization (MR) study using pooled data from genome-wide association studies of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) and AP patients. We evaluated the causal relationship between the GM and AP using methods such as inverse-variance weighting, MR-Egger, weighted medians, simple mode, and weighted mode. Cochran Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to examine the heterogeneity, multipotency, and outlier values of the variables, respectively. The reverse causal relationship between AP and the GM was assessed with reverse MR. In total, 5 gut microbial taxa were significantly associated with AP. The inverse-variance weighting results indicated that Acidaminococcaceae (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.66-1.00, P = .045) and Ruminococcaceae UCG004 (OR: 0.85, 95% CI: 0.72-0.99, P = .040) were protective factors against the occurrence of AP. Coprococcus 3 (OR: 1.32, 95% CI: 1.03-1.70, P = .030), Eisenbergiella (OR: 1.13, 95% CI: 1.00-1.28, P = .043), and the Eubacterium fissicatena group (OR: 1.18, 95% CI: 1.05-1.33, P = .006) were risk factors for the development of AP. A comprehensive sensitivity analysis proved our results to be reliable. Reverse MR analysis did not indicate any causal relationship between AP and the GM. This study revealed a complex causal relationship between 5 GM taxa and AP, providing new insights into the diagnostic and therapeutic potential of the GM in AP patients.
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Affiliation(s)
- Lin He
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Haojun Luo
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu Li
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Yan Zhang
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Li Peng
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Yan Xu
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Jing Lu
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Jinzhi Li
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
| | - Hang Liu
- Department of Pancreatitis Treatment Center, People’s Hospital of Deyang City, Deyang, China
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9
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Song K, Ling H, Wang L, Tian P, Jin X, Zhao J, Chen W, Wang G, Bi Y. Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice. Nutrients 2024; 16:1465. [PMID: 38794703 PMCID: PMC11124140 DOI: 10.3390/nu16101465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 05/08/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
Acute mountain sickness (AMS) is a common ailment in high-altitude areas caused by the body's inadequate adaptation to low-pressure, low-oxygen environments, leading to organ edema, oxidative stress, and impaired intestinal barrier function. The gastrointestinal tract, being the first to be affected by ischemia and hypoxia, is highly susceptible to injury. This study investigates the role of Lactobacillus delbrueckii subsp. bulgaricus in alleviating acute hypoxic-induced intestinal and tissue damage from the perspective of daily consumed lactic acid bacteria. An acute hypoxia mouse model was established to evaluate tissue injury, oxidative stress, inflammatory responses, and intestinal barrier function in various groups of mice. The results indicate that strain 4L3 significantly mitigated brain and lung edema caused by hypoxia, improved colonic tissue damage, and effectively increased the content of tight junction proteins in the ileum, reducing ileal permeability and alleviating mechanical barrier damage in the intestines due to acute hypoxia. Additionally, 4L3 helped to rebalance the intestinal microbiota. In summary, this study found that Lactobacillus delbrueckii subsp. bulgaricus strain 4L3 could alleviate acute intestinal damage caused by hypoxia, thereby reducing hypoxic stress. This suggests that probiotic lactic acid bacteria that exert beneficial effects in the intestines may alleviate acute injury under hypoxic conditions in mice, offering new insights for the prevention and treatment of AMS.
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Affiliation(s)
- Ke Song
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Hui Ling
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;
| | - Linlin Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Peijun Tian
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Xing Jin
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China; (K.S.); (L.W.); (P.T.); (X.J.); (J.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Yujing Bi
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;
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Li F, Wang Z, Cao Y, Pei B, Luo X, Liu J, Ge P, Luo Y, Ma S, Chen H. Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis. J Inflamm Res 2024; 17:2173-2193. [PMID: 38617383 PMCID: PMC11016262 DOI: 10.2147/jir.s448819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 03/20/2024] [Indexed: 04/16/2024] Open
Abstract
The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.
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Affiliation(s)
- Fan Li
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Zhengjian Wang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yinan Cao
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Boliang Pei
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Xinyu Luo
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Jin Liu
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Peng Ge
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Yalan Luo
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Shurong Ma
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
| | - Hailong Chen
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
- Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China
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11
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Yang W, Xi C, Yao H, Yuan Q, Zhang J, Chen Q, Wu G, Hu J. Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury. Front Cell Infect Microbiol 2024; 14:1304218. [PMID: 38352055 PMCID: PMC10861676 DOI: 10.3389/fcimb.2024.1304218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 01/16/2024] [Indexed: 02/16/2024] Open
Abstract
Objective The current study sought to clarify the role of lysozyme-regulated gut microbiota and explored the potential therapeutic effects of lysozyme on ileum injury induced by severe traumatic brain injury (sTBI) and bacterial pneumonia in vivo and in vitro experiments. Methods Male 6-8-week-old specific pathogen-free (SPF) C57BL/6 mice were randomly divided into Normal group (N), Sham group (S), sTBI group (T), sTBI + or Lysozyme-treated group (L), Normal + Lysozyme group (NL) and Sham group + Lysozyme group (SL). At the day 7 after establishment of the model, mice were anesthetized and the samples were collected. The microbiota in lungs and fresh contents of the ileocecum were analyzed. Lungs and distal ileum were used to detect the degree of injury. The number of Paneth cells and the expression level of lysozyme were assessed. The bacterial translocation was determined. Intestinal organoids culture and co-coculture system was used to test whether lysozyme remodels the intestinal barrier through the gut microbiota. Results After oral administration of lysozyme, the intestinal microbiota is rebalanced, the composition of lung microbiota is restored, and translocation of intestinal bacteria is mitigated. Lysozyme administration reinstates lysozyme expression in Paneth cells, thereby reducing intestinal permeability, pathological score, apoptosis rate, and inflammation levels. The gut microbiota, including Oscillospira, Ruminococcus, Alistipes, Butyricicoccus, and Lactobacillus, play a crucial role in regulating and improving intestinal barrier damage and modulating Paneth cells in lysozyme-treated mice. A co-culture system comprising intestinal organoids and brain-derived proteins (BP), which demonstrated that the BP effectively downregulated the expression of lysozyme in intestinal organoids. However, supplementation of lysozyme to this co-culture system failed to restore its expression in intestinal organoids. Conclusion The present study unveiled a virtuous cycle whereby oral administration of lysozyme restores Paneth cell's function, mitigates intestinal injury and bacterial translocation through the remodeling of gut microbiota.
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Affiliation(s)
- Weijian Yang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Caihua Xi
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Department of Neurosurgery and Neurocritical Care, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Haijun Yao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Department of Neurosurgery and Neurocritical Care, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qiang Yuan
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Jun Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Qifang Chen
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Department of Neurosurgery and Neurocritical Care, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Gang Wu
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Jin Hu
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
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Li X, Li Y, He C, Zhu Y. Bibliometric analysis of pancreatic diseases and gut microbiota research from 2002 to 2022. Heliyon 2024; 10:e23483. [PMID: 38187305 PMCID: PMC10767372 DOI: 10.1016/j.heliyon.2023.e23483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 12/03/2023] [Accepted: 12/05/2023] [Indexed: 01/09/2024] Open
Abstract
Background An increasing number of studies have indicated that pancreatic diseases are associated with the structure of the gut microbiota. We aimed to assess the research hotspots and trends in this field through a quantitative method. Materials and methods Articles related to pancreatic diseases and the gut microbiota published from 2002 to 2022 were retrieved from the Web of Science database. We visualized the countries/regions, institutions, authors, journals, and keywords using VOSviewer and CiteSpace software. The interplay between pancreatic diseases and the gut microbiota was also analysed. Results A total of 129 publications were finally identified. The number of papers increased gradually, and China held the dominant position with respect to publication output. Shanghai Jiao Tong University was the most influential institution. Zeng Yue ranked highest in the number of papers, and Scientific Reports was the most productive journal. The keywords "gut", "bacterial translocation", and "acute pancreatitis" appeared early for the first time, and "gut microbiota", "community", and "diversity" have been increasingly focused on. The predominant pancreatic disease correlated with the gut microbiota was pancreatic inflammatory disease (50.39%). Pancreatic diseases are associated with alterations in the gut microbiota, characterized by a decrease in beneficial bacteria and an increase in harmful bacteria. Conclusion This is the first comprehensive bibliometric analysis of all pancreatic diseases and the gut microbiota. The research on the relationship between them is still in the preliminary stage, and the trend is toward a gradual deepening of the research and precise treatment development. The interaction between the gut microbiota and pancreatic diseases will be of increasing concern in the future.
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Affiliation(s)
- Xin Li
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yu Li
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- HuanKui Academy, Nanchang University, Nanchang, China
| | - Cong He
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Zhang C, Li G, Lu T, Liu L, Sui Y, Bai R, Li L, Sun B. The Interaction of Microbiome and Pancreas in Acute Pancreatitis. Biomolecules 2023; 14:59. [PMID: 38254659 PMCID: PMC10813032 DOI: 10.3390/biom14010059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/24/2023] [Accepted: 12/28/2023] [Indexed: 01/24/2024] Open
Abstract
Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.
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Affiliation(s)
- Can Zhang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
| | - Guanqun Li
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
| | - Tianqi Lu
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
| | - Liwei Liu
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
| | - Yuhang Sui
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
| | - Rui Bai
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
| | - Le Li
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; (C.Z.)
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin 150001, China
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Zhao M, Cui M, Jiang Q, Wang J, Lu Y. Profile of Pancreatic and Ileal Microbiota in Experimental Acute Pancreatitis. Microorganisms 2023; 11:2707. [PMID: 38004720 PMCID: PMC10672832 DOI: 10.3390/microorganisms11112707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/18/2023] [Accepted: 10/19/2023] [Indexed: 11/26/2023] Open
Abstract
Acute pancreatitis (AP) is accompanied by gut microbiota dysbiosis. However, the composition of the pancreatic and ileal microbiota associated with AP is still unknown. This study aims to examine the alterations in the microbial composition of the pancreas and ileum in the context of experimental acute pancreatitis, as well as explore the potential interplay between these two regions. Methods: Caerulein (CAE), caerulein+lipopolysaccharide (CAE+LPS), and L-arginine (ARG) were used to induce AP in mice. The pancreas and ileum were collected for histological study and bacterial 16S rRNA gene sequencing. The results showed microbial structural segregation between the AP and control groups and between ARG and the two CAE groups (CAE, CAE+LPS) in the pancreas and ileum. Taxonomic analysis at the genus level and linear discriminant analysis effect size (LEfSe) at the operational taxonomic units (OTUs) level illustrated that AP mice exhibited a marked increase in the relative abundance of Muribaculaceae and a decrease in that of Dietzia both in the pancreas and ileum, and a reduction in Bifidobacterium only in the ileum; in addition, Roseburia was enriched in the two CAE groups in the pancreas and/or ileum, while Escherichia-Shigella expanded in the pancreas of the ARG group. Spearman correlation analysis between pancreatic and ileal microbiota revealed that the abundance of Muribaculaceae and Dietzia in the pancreas was related to that in the ileum. These findings demonstrated that caerulein and L-arginine differentially disturbed the pancreatic and ileal microbiota when inducing AP. Furthermore, these findings provide preliminary support for an association between the microbiota of the pancreas and ileum, which could be caused by AP-induced microbial translocation.
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Affiliation(s)
- Mengqi Zhao
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China; (M.Z.); (M.C.)
| | - Mengyan Cui
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China; (M.Z.); (M.C.)
| | - Qiaoli Jiang
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201812, China;
| | - Jingjing Wang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Yingying Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China; (M.Z.); (M.C.)
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201812, China;
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Zeng Z, Lin C, Zhang MC, Kossinna P, Wang P, Cao D, Wang J, Xu M, Wang X, Li Q, Xu X, Yang H, Zhu S, Liu GR, Xie K, Yang J, Luo Y, Wang Y, Zhang XH, Lin J, Chen H, Liu SL, Liu H. Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1. Phytother Res 2023; 37:4722-4739. [PMID: 37443453 DOI: 10.1002/ptr.7942] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/13/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023]
Abstract
Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.
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Affiliation(s)
- Zheng Zeng
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada
- School of Biomedical Science, The University of Hong Kong, Hong Kong
| | - Caiji Lin
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Meng-Chun Zhang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Pathum Kossinna
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada
| | - Pengfei Wang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Danli Cao
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Jiaxing Wang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Mengzhi Xu
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Xiaoyu Wang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Qing Li
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada
| | - Xiaohui Xu
- School of Basic Medicine, Harbin Medical University, Harbin, China
| | - Hao Yang
- Department of Pathology, Harbin Chest Hospital, Harbin, China
| | - Songling Zhu
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Gui-Rong Liu
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Kaihong Xie
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Jiaming Yang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Yao Luo
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Yao Wang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Xing-Hua Zhang
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Jingwen Lin
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Hang Chen
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
| | - Shu-Lin Liu
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
- National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD) College of Pharmacy, Harbin Medical University, Harbin, China
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada
| | - Huidi Liu
- Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China
- Harbin Medical University-University of Calgary Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University, Harbin, China
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada
- National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD) College of Pharmacy, Harbin Medical University, Harbin, China
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Cacciola NA, Venneri T, Salzano A, D'Onofrio N, Martano M, Saggese A, Vinale F, Neglia G, Campanile C, Baccigalupi L, Maiolino P, Cuozzo M, Russo R, Balestrieri ML, D'Occhio MJ, Ricca E, Borrelli F, Campanile G. Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis. Cell Commun Signal 2023; 21:245. [PMID: 37730576 PMCID: PMC10510155 DOI: 10.1186/s12964-023-01271-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 08/13/2023] [Indexed: 09/22/2023] Open
Abstract
BACKGROUND Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis. METHODS The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action. RESULTS Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling. CONCLUSIONS Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. Video Abstract.
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Affiliation(s)
- Nunzio Antonio Cacciola
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
| | - Tommaso Venneri
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano, 49, Naples, 80131, Italy
| | - Angela Salzano
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
| | - Nunzia D'Onofrio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio, 7, Naples, 80138, Italy
| | - Manuela Martano
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
| | - Anella Saggese
- Department of Biology, University of Naples Federico II, Via V. Cupa Cintia, 21, Naples, 80126, Italy
| | - Francesco Vinale
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
| | - Gianluca Neglia
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
| | - Ciro Campanile
- Institute of Genetics and Biophysics "A. Buzzati-Traverso", National Research Council (CNR-IGB), Via P. Castellino 111, Naples, 80131, Italy
| | - Loredana Baccigalupi
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini, 5, Naples, 80131, Italy
| | - Paola Maiolino
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
| | - Mariarosaria Cuozzo
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano, 49, Naples, 80131, Italy
| | - Roberto Russo
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano, 49, Naples, 80131, Italy
| | - Maria Luisa Balestrieri
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio, 7, Naples, 80138, Italy
| | - Michael John D'Occhio
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, New South Wales, 2006, Australia
| | - Ezio Ricca
- Department of Biology, University of Naples Federico II, Via V. Cupa Cintia, 21, Naples, 80126, Italy
| | - Francesca Borrelli
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano, 49, Naples, 80131, Italy.
| | - Giuseppe Campanile
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino, 1, Naples, 80137, Italy
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17
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Gao X, Hou MJ, Fu XY, Wang HC, Shang ZH, Zhu HD. Effect of replacing corn straw by sweet sorghum silage or whole plant corn silage in sheep diets on rumen fermentation and bacterial flora. Animal 2023; 17:100906. [PMID: 37556919 DOI: 10.1016/j.animal.2023.100906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 08/11/2023] Open
Abstract
Sweet sorghum silage (SS; Sorghum dochna 'Dochna') has been extensively studied in recent years as a supplementary forage-to-corn silage (CS; Zea mays L.), but there are still relatively few studies on its effects on the rumen environment of sheep. Determining the short-term impact of converting roughage from corn straws to SS compared to CS on rumen fermentation and bacterial population dynamics was the main goal of the current study. Twelve female thin-tailed Han sheep (29.8 ± 1.34 kg) were randomly divided into one of two treatments: concentrate supplemented with SS or CS, respectively. During the 15-day pretest period, concentrate was fed in two separate feedings at 0800 h and 1800 h, and ensure that the animals were all consumed within an hour of being fed. Thereafter, the animals had free access to corn straw. The feeding procedures during the pretest period were the same as during the measurement period. Rumen fluid was collected via sheep esophageal tube on the last day of adaptation phase (1-7 days) and stabilisation phase (8-30 days), respectively. The results showed that there was a similarity in the total concentration of VFA (volatile fatty acid) and the proportions of acetate, propionate, butyrate, and branched-chain VFA (P > 0.05) and microbial diversity indices (P > 0.05) between the two silage groups throughout the experimental period. The concentration of Ammonia nitrogen (P = 0.001) and proportion of valerate (P = 0.028) decreased in the CS and SS groups, respectively. The abundance and predicted function of rumen bacteria in the SS group did not differ significantly (P > 0.05) between the two measurement phases. However, the abundance of Prevotella_1 (P = 0.038) was higher in the CS group than in the SS group at 7 d. The abundances of Firmicutes (P = 0.005) and Ruminococcaceae_NK4A214_group (P = 0.002) increased, while the abundances of Bacteroidetes (P = 0.044), Proteobacteria (P = 0.046), and Prevotella_1 (P = 0.009) decreased in the CS group at 30 d. Genes related to pyruvate metabolism (P = 0.020) were significantly higher at 30 d than at 7 d, whereas purine metabolism (P = 0.007), pyrimidine metabolism (P = 0.007), and metabolic pathways (P = 0.010) were lower at 30 d in the CS group. In conclusion, this study indicated that SS maintained a steady rumen environment, while CS caused high fluctuations in bacterial abundance and predicted function for sheep.
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Affiliation(s)
- X Gao
- State Key Laboratory of Seed Innovation and Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, PR China; Engineering Research Center of Grassland Industry, Ministry of Education, Lanzhou University, Lanzhou 730020, PR China; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Lanzhou University, Lanzhou 730020, PR China
| | - M J Hou
- State Key Laboratory of Seed Innovation and Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, PR China; Engineering Research Center of Grassland Industry, Ministry of Education, Lanzhou University, Lanzhou 730020, PR China; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Lanzhou University, Lanzhou 730020, PR China
| | - X Y Fu
- State Key Laboratory of Seed Innovation and Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, PR China; Engineering Research Center of Grassland Industry, Ministry of Education, Lanzhou University, Lanzhou 730020, PR China; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Lanzhou University, Lanzhou 730020, PR China
| | - H C Wang
- State Key Laboratory of Seed Innovation and Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, PR China; Engineering Research Center of Grassland Industry, Ministry of Education, Lanzhou University, Lanzhou 730020, PR China; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Lanzhou University, Lanzhou 730020, PR China.
| | - Z H Shang
- State Key Laboratory of Seed Innovation and Grassland Agro-ecosystems, College of Ecology, Lanzhou University, Lanzhou 730000, PR China
| | - H D Zhu
- State Key Laboratory of Seed Innovation and Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, PR China; Engineering Research Center of Grassland Industry, Ministry of Education, Lanzhou University, Lanzhou 730020, PR China; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Lanzhou University, Lanzhou 730020, PR China
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18
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Huang Z, Wu H, Fan J, Mei Q, Fu Y, Yin N, Xu B, Luo S, Li B, Ni J, Huang C, Hu J, Zeng Y. Colonic mucin-2 attenuates acute necrotizing pancreatitis in rats by modulating intestinal homeostasis. FASEB J 2023; 37:e22994. [PMID: 37249555 DOI: 10.1096/fj.202201998r] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 04/25/2023] [Accepted: 05/12/2023] [Indexed: 05/31/2023]
Abstract
Mucin-2 (MUC2) secreted by goblet cells participates in the intestinal barrier, but its mechanism in acute necrotizing pancreatitis (ANP) remains unclear. In acute pancreatitis (AP) patients, the functions of goblet cells (MUC2, FCGBP, CLCA1, and TFF3) decreased, and MUC2 was negatively correlated with AP severity. ANP rats treated with pilocarpine (PILO) (PILO+ANP rats) to deplete MUC2 showed more serious pancreatic and colonic injuries, goblet cell dysfunction, gut dysbiosis, and bacterial translocation than those of ANP rats. GC-MS analysis of feces showed that PILO+ANP rats had lower levels of butyric acid, isobutyric acid, isovaleric acid, and hexanoic acid than those of ANP rats. The expression of MUC2 was associated with colonic injury and gut dysbiosis. All these phenomena could be relieved, and goblet cell functions were also partially reversed by MUC2 supplementation in ANP rats. TNF-α-treated colonoids had exacerbated goblet cell dysfunction. MUC2 expression was negatively correlated with the levels of pro-inflammatory cytokines (IL-1β and IL-6) (p < .05) and positively related to the expression of tight junction proteins (Claudin 1, Occludin, and ZO1) (p < .05). Downregulating MUC2 by siRNA increased the levels of the pro-inflammatory cytokines in colonoids. MUC2 might maintain intestinal homeostasis to alleviate ANP.
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Affiliation(s)
- Zehua Huang
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Huimin Wu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Junjie Fan
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Qixiang Mei
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yang Fu
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Nuoming Yin
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Binqiang Xu
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Shengzheng Luo
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Baiwen Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Jianbo Ni
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Chunlan Huang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Junjie Hu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yue Zeng
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
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19
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Zhao MQ, Cui MY, Jiang QL, Wang JJ, Fan MY, Lu YY. Characterization of Duodenal Microbiota in Patients with Acute Pancreatitis and Healthy Controls. Dig Dis Sci 2023:10.1007/s10620-023-07948-8. [PMID: 37258979 PMCID: PMC10352172 DOI: 10.1007/s10620-023-07948-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 04/04/2023] [Indexed: 06/02/2023]
Abstract
OBJECTIVE The small intestinal bacterial overgrowth (SIBO) in acute pancreatitis correlates with the severity of the disease. However, corresponding studies on the microbial composition of the duodenal mucosa of patients are uncommon. METHODS Duodenal mucosal biopsies were collected by gastroscopy from 16 patients with mild acute pancreatitis (the Ap group) and 16 healthy individuals (the control group) and subjected to histological studies as well as bacterial 16S rRNA gene sequencing. Caerulein and L-arginine were used to induce mild acute pancreatitis (MAP) and severe acute pancreatitis (SAP) in mice, respectively, and their pancreas and duodenum were collected for histological studies. RESULTS H&E analysis displayed no significant pathological damage in the descending duodenum of patients with acute pancreatitis compared with that of the controls. Immunofluorescence and Real-time PCR revealed that the expressions of tight junction proteins (TJPs) in duodenal mucosa were decreased in acute pancreatitis. The results of the alpha diversity analysis revealed no significant difference between the two groups, while LEfSe and the random forest revealed a few differences, indicating that the descending duodenum mucosal microbiota changed slightly in patients with mild acute pancreatitis. We observed the pathological changes and the expression of TJPs in the duodenum in the three groups of mice and found that SAP mice had more severe pathological damage in the duodenum. Furthermore, the expression of TJPs in the duodenum was lower in the MAP and SAP groups of mice compared to control mice, but it was similar in both groups. CONCLUSION Patients with mild acute pancreatitis had mild duodenal barrier dysfunction and slight changes in duodenal mucosal microbiota.
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Affiliation(s)
- Meng-Qi Zhao
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Meng-Yan Cui
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiao-Li Jiang
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Jing-Jing Wang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Miao-Yan Fan
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying-Ying Lu
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
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20
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De Lucia SS, Candelli M, Polito G, Maresca R, Mezza T, Schepis T, Pellegrino A, Zileri Dal Verme L, Nicoletti A, Franceschi F, Gasbarrini A, Nista EC. Nutrition in Acute Pancreatitis: From the Old Paradigm to the New Evidence. Nutrients 2023; 15:1939. [PMID: 37111158 PMCID: PMC10144915 DOI: 10.3390/nu15081939] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
The nutritional management of acute pancreatitis (AP) patients has widely changed over time. The "pancreatic rest" was the cornerstone of the old paradigm, and nutritional support was not even included in AP management. Traditional management of AP was based on intestinal rest, with or without complete parenteral feeding. Recently, evidence-based data underlined the superiority of early oral or enteral feeding with significantly decreased multiple-organ failure, systemic infections, surgery need, and mortality rate. Despite the current recommendations, experts still debate the best route for enteral nutritional support and the best enteral formula. The aim of this work is to collect and analyze evidence over the nutritional aspects of AP management to investigate its impact. Moreover, the role of immunonutrition and probiotics in modulating inflammatory response and gut dysbiosis during AP was extensively studied. However, we have no significant data for their use in clinical practice. This is the first work to move beyond the mere opposition between the old and the new paradigm, including an analysis of several topics still under debate in order to provide a comprehensive overview of nutritional management of AP.
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Affiliation(s)
- Sara Sofia De Lucia
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Marcello Candelli
- Department of Emergency, Anesthesiological and Reanimation Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Giorgia Polito
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Rossella Maresca
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Teresa Mezza
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Tommaso Schepis
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Antonio Pellegrino
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Lorenzo Zileri Dal Verme
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Alberto Nicoletti
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Francesco Franceschi
- Department of Emergency, Anesthesiological and Reanimation Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
| | - Enrico Celestino Nista
- Department of Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
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21
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Cui C, Wang X, Li L, Wei H, Peng J. Multifaceted involvements of Paneth cells in various diseases within intestine and systemically. Front Immunol 2023; 14:1115552. [PMID: 36993974 PMCID: PMC10040535 DOI: 10.3389/fimmu.2023.1115552] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 03/02/2023] [Indexed: 03/14/2023] Open
Abstract
Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn’s disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.
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Affiliation(s)
- Chenbin Cui
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Xinru Wang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Lindeng Li
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Hongkui Wei
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Jian Peng
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
- The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China
- *Correspondence: Jian Peng,
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Liu J, Lin H, Cao M, Lin T, Lin A, Xu W, Wang H, He J, Li Y, Tang H, Zhang B. Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT. Front Cell Infect Microbiol 2023; 13:1124256. [PMID: 36814445 PMCID: PMC9939747 DOI: 10.3389/fcimb.2023.1124256] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 01/16/2023] [Indexed: 02/09/2023] Open
Abstract
Background and Aims Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease. Methods We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota. Results We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group. Conclusion We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.
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Affiliation(s)
- Jinglong Liu
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Hao Lin
- Center for Microecological Medical Technology, Xiamen Institute of Union Respiratory Health, Xiamen, China
| | - Man Cao
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Tan Lin
- Center for Microecological Medical Technology, Xiamen Institute of Union Respiratory Health, Xiamen, China
| | - Aiqiang Lin
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Wei Xu
- Center for Microecological Medical Technology, Xiamen Institute of Union Respiratory Health, Xiamen, China
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Han Wang
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Jianquan He
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Yuantao Li
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- *Correspondence: Yuantao Li, ; Hailing Tang, ; Bangzhou Zhang,
| | - Hailing Tang
- Division of Gastroenterology, Xi’an Central Hospital, Xi’an, China
- *Correspondence: Yuantao Li, ; Hailing Tang, ; Bangzhou Zhang,
| | - Bangzhou Zhang
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- *Correspondence: Yuantao Li, ; Hailing Tang, ; Bangzhou Zhang,
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Hu X, Han Z, Zhou R, Su W, Gong L, Yang Z, Song X, Zhang S, Shu H, Wu D. Altered gut microbiota in the early stage of acute pancreatitis were related to the occurrence of acute respiratory distress syndrome. Front Cell Infect Microbiol 2023; 13:1127369. [PMID: 36949815 PMCID: PMC10025409 DOI: 10.3389/fcimb.2023.1127369] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/20/2023] [Indexed: 03/08/2023] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) is the most common cause of organ failure in acute pancreatitis (AP) patients, which associated with high mortality. Specific changes in the gut microbiota have been shown to influence progression of acute pancreatitis. We aimed to determine whether early alterations in the gut microbiota is related to and could predict ARDS occurrence in AP patients. Methods In this study, we performed 16S rRNA sequencing analysis in 65 AP patients and 20 healthy volunteers. The AP patients were further divided into two groups: 26 AP-ARDS patients and 39 AP-nonARDS patients based on ARDS occurrence during hospitalization. Results Our results showed that the AP-ARDS patients exhibited specific changes in gut microbiota composition and function as compared to subjects of AP-nonARDS group. Higher abundances of Proteobacteria phylum, Enterobacteriaceae family, Escherichia-Shigella genus, and Klebsiella pneumoniae, but lower abundances of Bifidobacterium genus were found in AP-ARDS group compared with AP-nonARDS groups. Random forest modelling analysis revealed that the Escherichia-shigella genus was effective to distinguish AP-ARDS from AP-nonARDS, which could predict ARDS occurrence in AP patients. Conclusions Our study revealed that alterations of gut microbiota in AP patients on admission were associated with ARDS occurrence after hospitalization, indicating a potential predictive and pathogenic role of gut microbiota in the development of ARDS in AP patients.
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Affiliation(s)
- Xiaomin Hu
- Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ziying Han
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruilin Zhou
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Wan Su
- Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Liang Gong
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zihan Yang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Song
- Department of Emergency Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Shuyang Zhang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Huijun Shu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Huijun Shu, ; Dong Wu,
| | - Dong Wu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Huijun Shu, ; Dong Wu,
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Huang B, Gui M, Ni Z, He Y, Zhao J, Peng J, Lin J. Chemotherapeutic Drugs Induce Different Gut Microbiota Disorder Pattern and NOD/RIP2/NF-κB Signaling Pathway Activation That Lead to Different Degrees of Intestinal Injury. Microbiol Spectr 2022; 10:e0167722. [PMID: 36222691 PMCID: PMC9769542 DOI: 10.1128/spectrum.01677-22] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 09/20/2022] [Indexed: 02/07/2023] Open
Abstract
5-Fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (L-OHP), and calcium folinate (CF) are widely used chemotherapeutic drugs to treat colorectal cancer. However, chemotherapeutic use is often accompanied by intestinal inflammation and gut microbiota disorder. Changes in gut microbiota may destroy the intestinal barrier, which contributes to the severity of intestinal injury. However, intestinal injury and gut microbiota disorder have yet to be compared among 5-FU, CPT-11, L-OHP, and CF in detail, thereby limiting the development of targeted detoxification therapy after chemotherapy. In this study, a model of chemotherapy-induced intestinal injury in tumor-bearing mice was established by intraperitoneally injecting chemotherapeutic drugs at a clinically equivalent dose. 16S rRNA gene sequencing was used to detect gut microbiota. We found that 5-FU, CPT-11, and l-OHP caused intestinal injury, inflammatory cytokine (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and IL-6) secretion, and gut microbiota disorder. We established a complex but clear network between the pattern of changes in gut microbiota and degree of intestinal damage induced by different chemotherapeutic drugs. L-OHP caused the most severe damage in the intestine and disorder of the gut microbiota and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Analysis by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt v.1.0) showed that the microbiota disorder pattern induced by 5-FU, CPT-11, and L-OHP was related to the NOD-like signaling pathway. Therefore, we detected the protein expression of the NOD/RIP2/NF-κB signaling pathway and found that L-OHP most activated this pathway. Redundancy analysis/canonical correlation analysis (RDA/CCA) revealed that Bifidobacterium, Akkermansia, Allobaculum, Catenibacterium, Mucispirillum, Turicibacter, Helicobacter, Proteus, Escherichia Shigella, Alloprevotealla, Vagococcus, Streptococcus, and "Candidatus Saccharimonas" were highly correlated with the NOD/RIP2/NF-κB signaling pathway and influenced by chemotherapeutic drugs. IMPORTANCE Chemotherapy-induced intestinal injury limits the clinical use of drugs. Intestinal injury involves multiple signaling pathways and gut microbiota disruption. Our results suggested that the degree of intestinal injury caused by different drugs of the first-line colorectal chemotherapy regimen is related to the pattern of changes in microbiota. The activation of the NOD/RIP2/NF-κB signaling pathway was also related to the pattern of changes in microbiota. l-OHP caused the most severe damage to the intestine and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Thirteen bacterial genera were related to different levels of intestinal injury and correlated with the NOD/RIP2/NF-κB pathway. Here, we established a network of different chemotherapeutic drugs, gut microbiota, and the NOD/RIP2/NF-κB signaling pathway. This study likely provided a new basis for further elucidating the mechanism and clinical treatment of intestinal injury caused by chemotherapy.
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Affiliation(s)
- Bin Huang
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Integrative Medicine of Fujian Province University, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Mengxuan Gui
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Zhuona Ni
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Yanbin He
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Jinyan Zhao
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Integrative Medicine of Fujian Province University, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Jun Peng
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Integrative Medicine of Fujian Province University, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Jiumao Lin
- Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Integrative Medicine of Fujian Province University, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
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Wang X, Zeng H, Xu J, Zhai Y, Xia H, Xi Y, Han Z. Characteristics of ruminal microbiota and metabolome in Holstein cows differing in milk protein concentrations. J Anim Sci 2022; 100:skac253. [PMID: 35938984 PMCID: PMC9645559 DOI: 10.1093/jas/skac253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 08/05/2022] [Indexed: 11/14/2022] Open
Abstract
The rumen is a vital organ containing vast amounts of microbes that play a key role in the digestion of nutrients and affect the production performance of ruminants. However, few studies have focused on the characterization of the ruminal microbiota composition and function in cows with long-term difference milk protein concentrations, and the relationship between milk protein concentration and ruminal microbiota remains elusive. In this study, we collected the data of milk protein concentrations of 1,025 Holstein cows for 10 mo on a commercial farm. Based on the milk protein concentrations, 30 cows were selected and divided into three groups (n = 10 per group): low milk protein group (LMP, milk protein concentration < 3.1%), medium milk protein group (MMP, 3.1% ≤ milk protein concentration < 3.4%), and high milk protein group (HMP, milk protein concentration ≥ 3.4%). The ruminal microbiome, metabolome, VFA concentrations and proportions, and amino acid profiles of the three groups were analyzed. The data showed that free amino acid (FAA) levels were lower in the rumen and higher in the plasma of HMP cows (P < 0.05). In addition, lower NH3 concentrations were observed in the rumen, plasma, and milk of the HMP cows (P < 0.05). Protease activity and isobutyric acid molar proportion in the rumen were lower in the HMP group (P < 0.05). Microbiome analysis showed that HMP cows had lower microbial diversity (represented as Shannon and Simpson indices) than LMP cows. At the genus level, lower relative abundances of Prevotella_1 and Ruminococcaceae_UCG_005 were observed in the HMP group (P < 0.05). At the operational taxonomic unit (OTU) level, a lower relative abundance of OTU3 (Prevotella ruminicola) was observed in the HMP group (P < 0.05). We found that the relative abundances of ruminal Prevotella_1 and OTU3 (Prevotella ruminicola) were negatively correlated with milk protein concentration (P < 0.05). These findings suggested that the cows with long-term high milk protein concentrations had lower microbial diversity and weaker protein degradation ability in the rumen. Furthermore, our observations identified a correlation between the milk protein concentration and ruminal microbiota.
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Affiliation(s)
- Xinling Wang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Hanfang Zeng
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Jie Xu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Yunfei Zhai
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Haibin Xia
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Yumeng Xi
- Key Laboratory of Crop and Animal Integrated Farming, Ministry of Agriculture, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China
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Tian M, Zhang G, Ding S, Jiang Y, Jiang B, Ren D, Chen P. Lactobacillus plantarum T3 as an adsorbent of aflatoxin B1 effectively mitigates the toxic effects on mice. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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Ye XX, Li KY, Li YF, Lu JN, Guo PT, Liu HY, Zhou LW, Xue SS, Huang CY, Fang SM, Gan QF. The effects of Clostridium butyricum on Ira rabbit growth performance, cecal microbiota and plasma metabolome. Front Microbiol 2022; 13:974337. [PMID: 36246250 PMCID: PMC9563143 DOI: 10.3389/fmicb.2022.974337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Clostridium butyricum (C. butyricum) can provide many benefits for animals’ growth performance and gut health. In this study, we investigated the effects of C. butyricum on the growth performance, cecal microbiota, and plasma metabolome in Ira rabbits. A total of 216 Ira rabbits at 32 days of age were randomly assigned to four treatments supplemented with basal diets containing 0 (CG), 200 (LC), 400 (MC), and 600 mg/kg (HC) C. butyricum for 35 days, respectively. In comparison with the CG group, C. butyricum supplementation significantly improved the average daily gain (ADG) and feed conversion rate (FCR) at 53 and 67 days of age (P < 0.05) and digestibilities of crude protein (CP) and crude fiber (CF) at 67 days of age (P < 0.05). The cellulase activity in the HC group was higher respectively by 50.14 and 90.13% at 53 and 67 days of age, than those in the CG groups (P < 0.05). Moreover, at 67 days of age, the diet supplemented with C. butyricum significantly increased the relative abundance of Verrucomicrobia at the phylum level (P < 0.05). Meanwhile, the concentrations of different metabolites, such as amino acids and purine, were significantly altered by C. butyricum (P < 0.05). In addition, 10 different genera were highly correlated with 52 different metabolites at 53-day-old and 6 different genera were highly correlated with 18 different metabolites at 67-day-old Ira rabbits. These findings indicated that the C. butyricum supplementation could significantly improve the growth performance by modifying the cecal microbiota structure and plasma metabolome of weaned Ira rabbits.
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Emerging Trends in Intestinal Knowledge Structure Associated With Acute Pancreatitis From 1981 to 2021: A Bibliometric Analysis. Pancreas 2022; 51:957-965. [PMID: 36607940 DOI: 10.1097/mpa.0000000000002140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES Bibliometric analysis has not comprehensively summarized studies of acute pancreatitis (AP)-associated intestinal diseases. This work aimed to evaluate cooperative networks of authors, countries, and institutions and explore the field's developing trends and hot topics. METHODS Original articles and reviews of AP-associated intestinal diseases were obtained from the Web of Science Core Collection on October 11, 2021. VOSviewer and CiteSpace software were used to perform co-occurrence analyses for authors, countries, and institutions and detect the highest citation burst. RESULTS A total of 1634 articles on the intestine associated with AP were identified. The United States, the University of Auckland, and Roland Andersson are the most influential country, research institute, and scholar, respectively. The World Journal of Gastroenterology (73 articles) has the highest number of publications, and Gastroenterology was the most co-cited journal. The top 5 key words are "acute pancreatitis," "bacterial translocation," "management," "gut," and "inflammatory bowel disease." We find that several emergent key words like "gut microbiota," "pathway," "gut barrier," "risk," and "oxidative stress" experienced a continuous and rapid development as new research directions. CONCLUSIONS This bibliometric study summarizes current important perspectives and offers comprehensive guidance on the AP-associated intestinal diseases, which may help researchers choose the most appropriate research directions.
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di Vito R, Conte C, Traina G. A Multi-Strain Probiotic Formulation Improves Intestinal Barrier Function by the Modulation of Tight and Adherent Junction Proteins. Cells 2022; 11:cells11162617. [PMID: 36010692 PMCID: PMC9406415 DOI: 10.3390/cells11162617] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/16/2022] [Accepted: 08/19/2022] [Indexed: 11/25/2022] Open
Abstract
In healthy individuals, tight junction proteins (TJPs) maintain the integrity of the intestinal barrier. Dysbiosis and increased intestinal permeability are observed in several diseases, such as inflammatory bowel disease. Many studies highlight the role of probiotics in preventing intestinal barrier dysfunction. The present study aims to investigate the effects of a commercially available probiotic formulation of L. rhamnosus LR 32, B. lactis BL 04, and B. longum BB 536 (Serobioma, Bromatech s.r.l., Milan, Italy) on TJPs and the integrity of the intestinal epithelial barrier, and the ability of this formulation to prevent lipopolysaccharide-induced, inflammation-associated damage. An in vitro model of the intestinal barrier was developed using a Caco-2 cell monolayer. The mRNA expression levels of the TJ genes were analyzed using real-time PCR. Changes in the amounts of proteins were assessed with Western blotting. The effect of Serobioma on the intestinal epithelial barrier function was assessed using transepithelial electrical resistance (TEER) measurements. The probiotic formulation tested in this study modulates the expression of TJPs and prevents inflammatory damage. Our findings provide new insights into the mechanisms by which probiotics are able to prevent damage to the gut epithelial barrier.
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Feng M, Hou T, Zhou M, Cen Q, Yi T, Bai J, Zeng Y, Liu Q, Zhang C, Zhang Y. Gut microbiota may be involved in Alzheimer’s disease pathology by dysregulating pyrimidine metabolism in APP/PS1 mice. Front Aging Neurosci 2022; 14:967747. [PMID: 35992591 PMCID: PMC9382084 DOI: 10.3389/fnagi.2022.967747] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/12/2022] [Indexed: 11/13/2022] Open
Abstract
IntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying the pathogenesis of AD aren’t completely clear. Studies have shown that the gut microbiota could be associated with AD pathogenesis; however, the pathways involved still need to be investigated.AimsTo explore the possible pathways of the involvement of gut microbiota in AD pathogenesis through metabolites and to identify new AD biomarkers.MethodsSeven-month-old APP/PS1 mice were used as AD models. The Morris water maze test was used to examine learning and memory ability. 16S rRNA gene sequencing and widely targeted metabolomics were used to identify the gut microbiota composition and fecal metabolic profile, respectively, followed by a combined analysis of microbiomics and metabolomics.ResultsImpaired learning abilities were observed in APP/PS1 mice. Statistically significant changes in the gut microbiota were detected, including a reduction in β-diversity, a higher ratio of Firmicutes/Bacteroidota, and multiple differential bacteria. Statistically significant changes in fecal metabolism were also detected, with 40 differential fecal metabolites and perturbations in the pyrimidine metabolism. Approximately 40% of the differential fecal metabolites were markedly associated with the gut microbiota, and the top two bacteria associated with the most differential metabolites were Bacillus firmus and Rikenella. Deoxycytidine, which causes changes in the pyrimidine metabolic pathway, was significantly correlated with Clostridium sp. Culture-27.ConclusionsGut microbiota may be involved in the pathological processes associated with cognitive impairment in AD by dysregulating pyrimidine metabolism. B. firmus, Rikenella, Clostridium sp. Culture-27, and deoxyuridine may be important biological markers for AD. Our findings provide new insights into the host-microbe crosstalk in AD pathology and contribute to the discovery of diagnostic markers and therapeutic targets for AD.
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Affiliation(s)
- Min Feng
- School of Rehabilitation Medicine and Healthcare, Hunan University of Medicine, Huaihua, China
| | - Tianshu Hou
- Department of Preventive Traditional Chinese Medicine, Chengdu Integrated TCM, Western Medical Hospital, Chengdu, China
| | - Mingze Zhou
- Health and Rehabilitation School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiuyu Cen
- Health and Rehabilitation School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ting Yi
- Health and Rehabilitation School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinfeng Bai
- School of Rehabilitation Medicine and Healthcare, Hunan University of Medicine, Huaihua, China
| | - Yun Zeng
- School of Rehabilitation Medicine and Healthcare, Hunan University of Medicine, Huaihua, China
| | - Qi Liu
- Acupuncture and Tuina School, Shaanxi University of Chinese Medicine, Xianyang, China
- *Correspondence: Qi Liu,
| | - Chengshun Zhang
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chengshun Zhang,
| | - Yingjun Zhang
- School of Clinical Medicine, Hunan University of Medicine, Huaihua, China
- Yingjun Zhang,
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Jing H, Chang Q, Xu Y, Wang J, Wu X, Huang J, Wang L, Zhang Z. Effect of aging on acute pancreatitis through gut microbiota. Front Microbiol 2022; 13:897992. [PMID: 35966681 PMCID: PMC9366017 DOI: 10.3389/fmicb.2022.897992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 07/11/2022] [Indexed: 11/30/2022] Open
Abstract
Background Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon. Methods Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction. Results The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not. Conclusion Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.
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Affiliation(s)
- Hui Jing
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Qimeng Chang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Yayun Xu
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jianfa Wang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Xubo Wu
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Jiating Huang
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Lishun Wang
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- Lishun Wang,
| | - Ziping Zhang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- *Correspondence: Ziping Zhang,
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Guo J, Xu F, Xie Y, Chen B, Wang Y, Nie W, Zhou K, Zhou H, Xu B. Effect of Xuanwei Ham Proteins with Different Ripening Periods on Lipid Metabolism, Oxidative Stress and Gut Microbiota in Mice. Mol Nutr Food Res 2022; 66:e2101020. [DOI: 10.1002/mnfr.202101020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 06/19/2022] [Indexed: 11/12/2022]
Affiliation(s)
- Jie Guo
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Feiran Xu
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
- Anhui Qingsong Food Co., Ltd. No.28 Ningxi Road Hefei 231299 China
| | - Yong Xie
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Bo Chen
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Ying Wang
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Wen Nie
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Kai Zhou
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Hui Zhou
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
| | - Baocai Xu
- School of Food and Biological Engineering Hefei University of Technology Hefei 230601 China
- Engineering Research Center of Bio‐process Ministry of Education Hefei University of Technology Hefei 230601 China
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Biliary Drainage Reduces Intestinal Barrier Damage in Obstructive Jaundice by Regulating Autophagy. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:3301330. [PMID: 35909583 PMCID: PMC9307405 DOI: 10.1155/2022/3301330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/21/2022] [Accepted: 06/29/2022] [Indexed: 11/25/2022]
Abstract
This study aims to investigate the mechanism by which biliary drainage reduces intestinal barrier damage in obstructive jaundice (OJ). A biliary drainage model was established in rats with OJ to detect changes in inflammatory factors and diamine oxidase (DAO), a marker of intestinal mucosal damage. The expression of autophagy-related genes in the intestinal mucosa after biliary drainage was detected using a reverse transcription-polymerase chain reaction. The rats were separated into two groups that received the autophagy activator rapamycin (RAPA) or the autophagy inhibitor 3-methyladenine (3-MA) to further investigate whether biliary drainage could alleviate the inflammatory response, oxidative stress, mitochondrial complex IV damage, and thus barrier damage in rats with OJ. The expression levels of inflammatory factors and the serum DAO content were increased in rats with OJ (P < 0.05). Biliary drainage further induced autophagy, reduced the expression levels of inflammatory factors, decreased the serum DAO content (P < 0.05), and improved intestinal mucosal damage. Administration of RAPA to OJ rats with biliary drainage increased autophagy (P < 0.05); decreased inflammatory factor secretion (P < 0.05), the serum DAO content (P < 0.05), oxidative stress (P < 0.05), and mitochondrial respiratory chain complex IV damage (P < 0.05); and ameliorated intestinal mucosal injury in OJ rats. When OJ rats were treated with 3-MA, intestinal mucosal injury, intestinal mitochondrial injury, and oxidative stress were all aggravated (P < 0.05). Biliary drainage can reduce the expression of inflammatory factors, oxidative stress, and mitochondrial injury by inducing intestinal mucosal autophagy in OJ rats, thus suggesting its role in the alleviation of intestinal mucosal injury.
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Jiao J, Liu J, Li Q, Zhang G, Pan C, Luo F, Zhang Q, Qi B, Zhao L, Yin P, Shang D. Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis. Front Cell Infect Microbiol 2022; 12:838340. [PMID: 35811665 PMCID: PMC9257083 DOI: 10.3389/fcimb.2022.838340] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 05/02/2022] [Indexed: 11/18/2022] Open
Abstract
Impaired intestinal barrier function and gut microbiota dysbiosis are believed to be related to exacerbation of acute pancreatitis (AP). As a bacterial cell wall peptidoglycan component, diaminopimelic acid (DAP) is a specific ligand of NOD1 that regulates the NOD1/RIP2/NF-kB signaling pathway. Here, we investigated the role of DAP in the crosstalk between the gut microbiota and pancreas during the occurrence of AP. Upregulation of NOD1/RIP2/NF-kB and elevated serum DAP levels were found in severe AP (SAP) model rats. The accumulation of DAP in SAP patients corroborated its ability to serve as an indicator of disease severity. Subsequently, SAP rats were treated with oral administration of the traditional Chinese medicine Qingyi Keli (QYKL) as well as neomycin, which can widely eliminate DAP-containing bacteria. Both QYKL and neomycin intervention ameliorated intestinal and pancreatic damage and systemic inflammation in SAP rats. Through 16S rDNA sequencing, we found that QYKL could rehabilitate the gut microbiota structure and selectively inhibit the overgrowth of enteric bacteria, such as Helicobacter and Lactobacillus, in SAP rats without affecting some protective strains, including Romboutsia and Allobaculum. Interestingly, we demonstrated that the decrease in serum DAP was accompanied by suppression of the NOD1/RIP2/NF-kB signaling pathway in both the intestine and pancreas of the two intervention groups. Taken together, these results suggested that the gut microbiota-DAP-NOD1/RIP2 signaling pathway might play a critical role in the progression of AP and that SAP could be alleviated via intervention in the signaling pathway. Our work provides new potential early warning indicators of SAP and targets for intervention.
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Affiliation(s)
- Juying Jiao
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianjun Liu
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Qi Li
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
| | - Guixin Zhang
- Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Chen Pan
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Fei Luo
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Qingkai Zhang
- Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Bing Qi
- Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Liang Zhao
- Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Peiyuan Yin
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
- *Correspondence: Dong Shang, ; Peiyuan Yin,
| | - Dong Shang
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Integrative Medicine, Dalian Medical University, Dalian, China
- Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Dong Shang, ; Peiyuan Yin,
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Ma Y, Lu C, Ji B, Qin J, Cai C, Yang Y, Zhao Y, Liang G, Guo X, Cao G, Li B, Gao P. Integrated Omics Analysis Reveals Alterations in the Intestinal Microbiota and Metabolites of Piglets After Starvation. Front Microbiol 2022; 13:881099. [PMID: 35783381 PMCID: PMC9240708 DOI: 10.3389/fmicb.2022.881099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/11/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is a serious public health problem. Short-term starvation is an effective way to lose weight but can also cause harm to the body. However, a systematic assessment of the relationship between the intestinal microbiota and metabolites after complete fasting is lacking. Pigs are the best animal models for exploring the mechanisms of human nutrition digestion and absorption, metabolism, and disease treatment. In this study, 16S rRNA sequencing and liquid chromatography-mass spectrometry were used to analyze the changes in the intestinal microbiota and metabolite profiles in piglets under starvation stress. The results show that the microbial composition was changed significantly in the starvation groups compared with the control group (P < 0.05), suggesting that shifts in the microbial composition were induced by starvation stress. Furthermore, differences in the correlation of the intestinal microbiota and metabolites were observed in the different experimental groups. Starvation may disrupt the homeostasis of the intestinal microbiota and metabolite profile and affect the health of piglets. However, piglets can regulate metabolite production to compensate for the effects of short-term starvation. Our results provide a background to explore the mechanism of diet and short-term hunger for intestinal homeostasis.
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Wang Z, Li F, Liu J, Luo Y, Guo H, Yang Q, Xu C, Ma S, Chen H. Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury. Front Immunol 2022; 13:913178. [PMID: 35774796 PMCID: PMC9237221 DOI: 10.3389/fimmu.2022.913178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/11/2022] [Indexed: 11/28/2022] Open
Abstract
Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.
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Affiliation(s)
- Zhengjian Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Fan Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jin Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Haoya Guo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qi Yang
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, United States
| | - Shurong Ma
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Shurong Ma, ; Hailong Chen,
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Shurong Ma, ; Hailong Chen,
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Abstract
We demonstrate that AP patients and experimental AP mice exhibited a dysfunction of Paneth cells. Our
in vivo
research showed that the severity of AP was exacerbated by the long-term dysfunction of Paneth cells, which was associated with gut microbiota disorder.
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Qin D, Bai Y, Li Y, Huang Y, Li L, Wang G, Qu Y, Wang J, Yu LY, Hou X. Changes in Gut Microbiota by the Lactobacillus casei Anchoring the K88 Fimbrial Protein Prevented Newborn Piglets From Clinical Diarrhea. Front Cell Infect Microbiol 2022; 12:842007. [PMID: 35372106 PMCID: PMC8972131 DOI: 10.3389/fcimb.2022.842007] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 02/21/2022] [Indexed: 12/30/2022] Open
Abstract
In the last 20 years, accumulating evidence indicates that the gut microbiota contribute to the development, maturation, and regulation of the host immune system and mediate host anti-pathogen defenses. Lactobacillus casei (L.casei) is a normal flora of the gastrointestinal tract in mammals and, as a great mucosal delivery vehicle, has wide use in bioengineering. However, the diarrhea prevention role of commensal intestinal microbiota interfered by the recombinant L.casei (rL.casei) in newborn piglets is not well understood. In our study, newborn piglets orally fed with the rL.casei surface displayed the fimbrial protein K88 of enterotoxigenic Escherichia coli (ETEC) and their feces were collected for a period of time after feeding. The next-generation sequencing of these fecal samples showed that the relative abundance of L.casei was significantly increased. The oral administration of rL.casei altered the intestinal microbial community as evidenced by altered microbial diversity and microbial taxonomic composition. Remarkably, the functional enhancing of the intestinal bacterial community by rL.casei was positively correlated with membrane transport, replication, and repair (p < 0.05). The specific antibody detection indicates that high levels of anti-K88 secretory immunoglobulin A (sIgA) were induced in fecal samples and systemic immunoglobulin G was produced in serum. The diarrhea rate in piglets caused by ETEC K88 was decreased by about 24%. Thus, the oral administration of rL.casei not only activated the mucosal and humoral immune responses in vivo but also contributed to shape the intestinal probiotics in newborn piglets and to significantly reduce the diarrhea rates of newborn piglets.
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Affiliation(s)
- Da Qin
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Yongfei Bai
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Yan Li
- Colleges of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Yanmei Huang
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Liyang Li
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Guihua Wang
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Yi Qu
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Jiabin Wang
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Li-Yun Yu
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
- Colleges of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
- *Correspondence: Li-Yun Yu, ; Xilin Hou,
| | - Xilin Hou
- Colleges of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China
- *Correspondence: Li-Yun Yu, ; Xilin Hou,
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De Pastena M, Paiella S, Fontana M, Filippini C, Addari L, Giorgi A, Canton S, Zanusso G, Azzini AM, Bassi C, Tacconelli E, Salvia R. The clinical and economic impact of surgical site infections after distal pancreatectomy. Surgery 2022; 171:1652-1657. [PMID: 34972593 DOI: 10.1016/j.surg.2021.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 10/20/2021] [Accepted: 11/11/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND The present study aimed to evaluate surgical site infections' clinical and economic impact after distal pancreatectomy. METHODS The study was a prospective, monocentric, observational study, including all adult patients who underwent distal pancreatectomy. According to the American Centers for Disease Control and Prevention definition, the surgical site infection assessment was prospectively performed by trained personnel. The Accordion Severity Grading System was used to evaluate the clinical burden of surgical site infection. The hospitalization's total costs were calculated using the hospital expenditure report, excluding the intraoperative costs. RESULTS During the study period, 414 distal pancreatectomies were performed. The overall incidence of surgical site infection was 26% (106 patients). Surgical site infections were associated with a higher body mass index (P = .022, odds ratio 1.2), positive preoperative rectal swab for multidrug resistant bacteria (P = .010, odds ratio 4.2), and increased operative time (P = .037, odds ratio 1.1). Using the Accordion Severity Grading System, surgical site infections contributed significantly to the total clinical burden (25.5%) and prolonged hospitalization (P < .001). Furthermore, surgical site infection doubled the costs (12.915 vs 6.888 euros, P < .001). CONCLUSION Surgical site infection has a high clinical burden, negatively impacting the postoperative course. The costs and length of stay proportionally increased with the surgical site infection severity, doubling the hospitalization expenses.
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Affiliation(s)
- Matteo De Pastena
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Michele Fontana
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Chiara Filippini
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Laura Addari
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Alice Giorgi
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Simona Canton
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Giovanni Zanusso
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Anna Maria Azzini
- Infectious Diseases Unit, Department of Diagnostic and Public Health, University of Verona, Italy
| | - Claudio Bassi
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy
| | - Evelina Tacconelli
- Infectious Diseases Unit, Department of Diagnostic and Public Health, University of Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy.
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Tao J, Cheema H, Kesh K, Dudeja V, Dawra R, Roy S. Chronic pancreatitis in a caerulein-induced mouse model is associated with an altered gut microbiome. Pancreatology 2022; 22:30-42. [PMID: 34949545 PMCID: PMC8748396 DOI: 10.1016/j.pan.2021.12.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 10/29/2021] [Accepted: 12/12/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Chronic pancreatitis (CP) is an inflammatory disease of the pancreas with loss of exocrine/endocrine functions as well as development of fibrosis. Dysbiosis of gut microbiome has been shown to be involved in the pathogenesis of many disease processes. Therefore, we aim to investigate the alteration in gut microbiome associated with CP in caerulein-induced mouse model. METHODS CP was induced in C57Bl/6 by using caerulein injections (50 μg/kg/h, i.p., x7, twice weekly for 10 weeks). Stool samples were collected either one week after end of injection (10-week CP) or 6 weeks (16-week CP). DNA was extracted from stool samples and V4 region of 16S rDNA was sequenced for microbiome analysis. RESULTS CP was strongly associated with the alteration in the composition of the gut microbiome, evidenced by differences in α and β diversity. When β diversity was measured using both weighted and unweighted UniFrac distances, stool from control mice is significantly different from mice on 10-week or 16-week CP (q < 0.01). The α-diversity measured by Faith's phylogenetic diversity was lowest in stool from healthy control and highest in stool from mice with 16-week CP (p < 0.001). Bacteria taxa differentially enriched in CP samples were detected using linear discriminant analysis. Bacteria from genera Bifidobacterium, Akkermansia, and Desulfovibrio were enriched in samples from 10-week CP mice. Bacteria from genera Allobaculum, Prevotella, and Bacteroides were enriched in samples from 16-week CP mice. CONCLUSION Together, these analyses reveal pronounced alteration in the gut microbiome composition, diversity, and function when mice develop CP.
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Affiliation(s)
- J Tao
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA
| | - H Cheema
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA
| | - K Kesh
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA
| | - V Dudeja
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA
| | - R Dawra
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.
| | - S Roy
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.
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Xie Y, Sun J, Hu C, Ruan B, Zhu B. Oral Microbiota Is Associated With Immune Recovery in Human Immunodeficiency Virus-Infected Individuals. Front Microbiol 2021; 12:794746. [PMID: 34956162 PMCID: PMC8696184 DOI: 10.3389/fmicb.2021.794746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022] Open
Abstract
The role of the oral microbiota in HIV-infected individuals deserves attention as either HIV infection or antiretroviral therapy (ART) may have effect on the diversity and the composition of the oral microbiome. However, few studies have addressed the oral microbiota and its interplay with different immune responses to ART in HIV-infected individuals. Salivary microbiota and immune activation were studied in 30 HIV-infected immunological responders (IR) and 34 immunological non-responders (INR) (≥500 and < 200 CD4 + T-cell counts/μl after 2 years of HIV-1 viral suppression, respectively) with no comorbidities. Metagenome sequencing revealed that the IR and the INR group presented similar salivary bacterial richness and diversity. The INR group presented a significantly higher abundance of genus Selenomonas_4, while the IR group manifested higher abundances of Candidatus_Saccharimonas and norank_p_Saccharimonas. Candidatus_Saccharimonas and norank_p_Saccharimonas were positively correlated with the current CD4 + T-cells. Candidatus_Saccharimonas was positively correlated with the markers of adaptive immunity CD4 + CD57 + T-cells, while negative correlation was found between norank _p_Saccharimonas and the CD8 + CD38 + T-cells as well as the CD4/CD8 + HLADR + CD38 + T-cells. The conclusions are that the overall salivary microbiota structure was similar in the immunological responders and immunological non-responders, while there were some taxonomic differences in the salivary bacterial composition. Selenomona_4, Candidatus_Saccharimonas, and norank _p_Saccharimonas might act as important factors of the immune recovery in the immunodeficiency patients, and Candidatus_Saccharimonas could be considered in the future as screening biomarkers for the immune responses in the HIV-infected individuals.
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Affiliation(s)
- Yirui Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Jia Sun
- Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Caiqin Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Biao Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
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Guo C, Liu X, Xu Y, Han X, Xie R, Meng X, Li Y, Chen T, Cheng Z, Fu X. Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique. Front Cell Dev Biol 2021; 9:778826. [PMID: 34926462 PMCID: PMC8672438 DOI: 10.3389/fcell.2021.778826] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 11/02/2021] [Indexed: 12/22/2022] Open
Abstract
Background: Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques. Method: The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined. Results: A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation in vitro, and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level. Conclusion: CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.
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Affiliation(s)
- Cui Guo
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Graduate School of Liaoning University of traditional Chinese Medicine, Shenyang, China
| | - Xiaoqiang Liu
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Department of Pain, Shibei Hospital, Shanghai, China
| | - Yimin Xu
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinyue Han
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Runnan Xie
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Miaohang Town Community Health Service Center, Shanghai, China
| | - Xiangxue Meng
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Graduate School of Liaoning University of traditional Chinese Medicine, Shenyang, China
| | - Yuan Li
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tongyu Chen
- Cardiothoracic Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhihong Cheng
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering Research Center, Shanghai, China
| | - Xiaoling Fu
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Kong C, Akkerman R, Klostermann CE, Beukema M, Oerlemans MMP, Schols HA, de Vos P. Distinct fermentation of human milk oligosaccharides 3-FL and LNT2 and GOS/inulin by infant gut microbiota and impact on adhesion of Lactobacillus plantarum WCFS1 to gut epithelial cells. Food Funct 2021; 12:12513-12525. [PMID: 34811557 DOI: 10.1039/d1fo02563e] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Human milk oligosaccharides (hMOs) are unique bioactive components in human milk. 3-Fucosyllactose (3-FL) is an abundantly present hMO that can be produced in sufficient amounts to allow application in infant formula. Lacto-N-triaose II (LNT2) can be obtained by acid hydrolysis of lacto-N-neotetraose (LNnT). Both 3-FL and LNT2 have been shown to have health benefits, but their impact on infant microbiota composition and microbial metabolic products such as short-chain fatty acids (SCFAs) is unknown. To gain more insight in fermentability, we performed in vitro fermentation studies of 3-FL and LNT2 using pooled fecal microbiota from 12-week-old infants. The commonly investigated galacto-oligosaccharides (GOS)/inulin (9 : 1) served as control. Compared to GOS/inulin, we observed a delayed utilization of 3-FL, which was utilized at 60.3% after 36 h of fermentation, and induced the gradual production of acetic acid and lactic acid. 3-FL specifically enriched bacteria of Bacteroides and Enterococcus genus. LNT2 was fermented much faster. After 14 h of fermentation, 90.1% was already utilized, and production of acetic acid, succinic acid, lactic acid and butyric acid was observed. LNT2 specifically increased the abundance of Collinsella, as well as Bifidobacterium. The GOS present in the GOS/inulin mixture was completely fermented after 14 h, while for inulin, only low DP was rapidly utilized after 14 h. To determine whether the fermentation might lead to enhanced colonization of commensal bacteria to gut epithelial cells, we investigated adhesion of the commensal Lactobacillus plantarum WCFS1 to Caco-2 cells. The fermentation digesta of LNT2 collected after 14 h, 24 h, and 36 h, and GOS/inulin after 24 h of fermentation significantly increased the adhesion of L. plantarum WCFS1 to Caco-2 cells, while 3-FL had no such effect. Our findings illustrate that fermentation of hMOs is very structure-dependent and different from the commonly applied GOS/inulin, which might lead to differential potencies to stimulate adhesion of commensal cells to gut epithelium and consequent microbial colonization. This knowledge might contribute to the design of tailored infant formulas containing specific hMO molecules to meet the need of infants during the transition from breastfeeding to formula.
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Affiliation(s)
- Chunli Kong
- School of Food and Health, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China. .,Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
| | - Renate Akkerman
- Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
| | - Cynthia E Klostermann
- Biobased Chemistry and Technology, Wageningen University & Research, Wageningen, The Netherlands
| | - Martin Beukema
- Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
| | - Marjolein M P Oerlemans
- Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
| | - Henk A Schols
- Laboratory of Food Chemistry, Wageningen University & Research, Wageningen, The Netherlands
| | - Paul de Vos
- Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
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An L, Wuri J, Zheng Z, Li W, Yan T. Microbiota modulate Doxorubicin induced cardiotoxicity. Eur J Pharm Sci 2021; 166:105977. [PMID: 34416387 DOI: 10.1016/j.ejps.2021.105977] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/31/2021] [Accepted: 08/15/2021] [Indexed: 01/14/2023]
Abstract
Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2-3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis, inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG-001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.
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Affiliation(s)
- Lulu An
- Neurology, Tianjin Medical University General Hospital Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin-300052, China.
| | - Jimusi Wuri
- Neurology, Tianjin Medical University General Hospital Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin-300052, China.
| | - Zhitong Zheng
- Neurology, Tianjin Medical University General Hospital Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin-300052, China.
| | - Wenqui Li
- Neurology, Tianjin Medical University General Hospital Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin-300052, China.
| | - Tao Yan
- Neurology, Tianjin Medical University General Hospital Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin-300052, China.
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Takauji S, Konishi H, Fujiya M, Ueno N, Tanaka H, Sato H, Isozaki S, Kashima S, Moriichi K, Mizukami Y, Okumura T. Polyphosphate, Derived from Lactobacillus brevis, Modulates the Intestinal Microbiome and Attenuates Acute Pancreatitis. Dig Dis Sci 2021; 66:3872-3884. [PMID: 33492535 DOI: 10.1007/s10620-020-06747-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 11/23/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. AIMS We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. METHODS Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. RESULTS The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. CONCLUSIONS Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.
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Affiliation(s)
- Shuhei Takauji
- Department of Emergency Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Hiroaki Konishi
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Mikihiro Fujiya
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan.
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan.
| | - Nobuhiro Ueno
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Hiroki Tanaka
- Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Hiroki Sato
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Shotaro Isozaki
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Shin Kashima
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Kentaro Moriichi
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Yusuke Mizukami
- Cancer Genetics, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan
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Ye S, Si C, Deng J, Chen X, Kong L, Zhou X, Wang W. Understanding the Effects of Metabolites on the Gut Microbiome and Severe Acute Pancreatitis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:1516855. [PMID: 34712726 PMCID: PMC8548099 DOI: 10.1155/2021/1516855] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 10/09/2021] [Indexed: 12/11/2022]
Abstract
Acute pancreatitis (AP) is an inflammatory disease of the pancreas. The severity is classified as mild (MAP), moderately severe (MSAP), or severe (SAP). In patients with SAP, organ dysfunction can occur in the early stage of the disease course, accompanied by secondary infection, with a mortality rate of 36%-50%. In the late stage SAP, infection-related complications caused by pancreatic necrotic tissue and peripancreatic effusion are the main causes of death in patients. Dysbacteriosis of intestinal microflora, barrier dysfunction of intestinal mucosa, and translocation of enteric bacteria are considered to be the main causes of infection of pancreatic necrotic tissue and peripancreatic effusion. During the past few years, increasing attention has been paid to the metabolic activities of intestinal microflora in SAP, which plays an important role in the metabolic activities of the human body. This review is aimed at bringing together the most recent findings and advances regarding the gut microbial community and associated gut microbial community metabolites and illustrating the role of these metabolites in disease progression in severe acute pancreatitis. We hope that this review will provide new ideas and schemes for the treatment of SAP in the clinical settings.
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Affiliation(s)
- Shijie Ye
- Wenzhou Medical University, Wenzhou, China
| | - Chenli Si
- Wenzhou Medical University, Wenzhou, China
| | - Jie Deng
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Xiaohu Chen
- Department of Pathology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | | | - Xiang Zhou
- Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Weiming Wang
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Guo C, Xu Y, Han X, Liu X, Xie R, Cheng Z, Fu X. Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice. Front Oncol 2021; 11:736225. [PMID: 34513713 PMCID: PMC8427437 DOI: 10.3389/fonc.2021.736225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 08/09/2021] [Indexed: 12/30/2022] Open
Abstract
Objective To screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology. Methods The molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD. Results The general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis. Conclusion The pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.
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Affiliation(s)
- Cui Guo
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yimin Xu
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinyue Han
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoqiang Liu
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Department of Pain, Shibei Hospital, Shanghai, China
| | - Runnan Xie
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Department of Traditional Chinese Medicine, Miaohang Town Community Health Service Center, Shanghai, China
| | - Zhihong Cheng
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering Research Center, Shanghai, China
| | - Xiaoling Fu
- Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Gut microbiota in pancreatic diseases: possible new therapeutic strategies. Acta Pharmacol Sin 2021; 42:1027-1039. [PMID: 33093569 DOI: 10.1038/s41401-020-00532-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022]
Abstract
Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential molecular mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clinical potential to reduce the cost of pancreatic diseases.
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Zhu Y, Mei Q, Fu Y, Zeng Y. Alteration of gut microbiota in acute pancreatitis and associated therapeutic strategies. Biomed Pharmacother 2021; 141:111850. [PMID: 34214727 DOI: 10.1016/j.biopha.2021.111850] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/21/2021] [Accepted: 06/24/2021] [Indexed: 01/06/2023] Open
Abstract
Gut microbiome is considered as a crucial regulator of human health. Alteration of gut microbiome has been reported in acute pancreatitis (AP) and probably contributes to the severity of disease. Explore the precise role of gut microbiome in the pathogenesis of AP could offer new strategies to improve the clinical outcomes of AP. This review summarizes the role of gut microbiome in AP, lists possible mechanisms associated with it and offers an overview of current treatments based on gut microbiome.
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Affiliation(s)
- Ying Zhu
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China; Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China
| | - Qixiang Mei
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China; Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China
| | - Yang Fu
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China; Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China
| | - Yue Zeng
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201600, China.
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Huang SQ, Wen Y, Sun HY, Deng J, Zhang YL, Huang QL, Wang B, Luo ZL, Tang LJ. Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway. World J Gastroenterol 2021; 27:815-834. [PMID: 33727772 PMCID: PMC7941863 DOI: 10.3748/wjg.v27.i9.815] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/14/2020] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood.
AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms.
METHODS SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed.
RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury.
CONCLUSION APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.
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Affiliation(s)
- Shang-Qing Huang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Yi Wen
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Hong-Yu Sun
- Basic Medical Laboratory, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Jie Deng
- Department of Clinical Pharmacy, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Yao-Lei Zhang
- Basic Medical Laboratory, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Qi-Lin Huang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Bing Wang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Zhu-Lin Luo
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Li-Jun Tang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
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