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Feng Y, Chen W, Chen J, Sun F, Kong F, Li L, Zhao Y, Wu S, Li Z, Du Y, Kong X. Dietary emulsifier carboxymethylcellulose-induced gut dysbiosis and SCFA reduction aggravate acute pancreatitis through classical monocyte activation. MICROBIOME 2025; 13:83. [PMID: 40128912 PMCID: PMC11931840 DOI: 10.1186/s40168-025-02074-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 02/27/2025] [Indexed: 03/26/2025]
Abstract
OBJECTIVE Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation. DESIGN C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed. RESULTS CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients. CONCLUSIONS This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.
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Affiliation(s)
- Yongpu Feng
- National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China
- Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China
| | - Wenjin Chen
- Department of Urology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China
| | - Jiayu Chen
- Changhai Clinical Research Unit, Naval Medical University, Shanghai, 200433, People's Republic of China
| | - Fengyuan Sun
- National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China
- Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China
| | - Fanyang Kong
- National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China
- Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China
| | - Lei Li
- Digestive Endoscopy Center, Shanghai Tenth People'S Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - Yating Zhao
- National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China
| | - Shouxin Wu
- Shanghai Zhenwei Biotechnology Co., Ltd, Shanghai, 200245, China
| | - Zhaoshen Li
- Changhai Clinical Research Unit, Naval Medical University, Shanghai, 200433, People's Republic of China.
| | - Yiqi Du
- Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China.
| | - Xiangyu Kong
- National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, 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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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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Wu H, Wang M, Ren X, Li Z, Ai L, Xie F, Sun Z. Preparation of type 3 rice resistant starch using high-pressure homogenous coenzyme treatment and investigating its potential therapeutic effects on blood glucose and intestinal flora in db/db mice. Int J Biol Macromol 2024; 264:130552. [PMID: 38442835 DOI: 10.1016/j.ijbiomac.2024.130552] [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: 10/19/2023] [Revised: 01/16/2024] [Accepted: 02/28/2024] [Indexed: 03/07/2024]
Abstract
Resistant starch from rice was prepared using high-pressure homogenization and branched chain amylase treatment. The yield, starch external structure, thermal properties, and crystal structure of rice-resistant starch prepared in different ways were investigated. The results showed that the optimum homogenizing pressure was 90 MPa, the optimum digestion time was 4 h, the optimum concentration of branched-chain amylase was 50 U/g and the yield of resistant starch was 38.58 %. Scanning electron microscopy results showed a rougher surface and more complete debranching of the homogenized coenzyme rice-resistant starch granules. FT-IR and X-ray diffraction results showed that the homogenization treatment exhibited a spiral downward trend on rice starch relative crystallinity and a spiral upward trend on starch debranching and recrystallization. The 4-week dietary intervention in db/db type 2 diabetic mice showed that homogeneous coenzyme rice-resistant starch had a better glycemic modulating effect than normal debranched starch and had a tendency to interfere with the index of liver damage in T2DM mice. Additionally, homogeneous coenzyme rice-resistant starch proved more effective in improving intestinal flora disorders and enhancing the abundance of probiotics in T2DM mice.
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Affiliation(s)
- Haoming Wu
- Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, 201499 Shanghai, China; Shanghai Engineering Research Center of Food Microbiology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Man Wang
- Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, 201499 Shanghai, China
| | - Xiaolong Ren
- Shanghai Engineering Research Center of Food Microbiology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Zhipeng Li
- Shanghai Engineering Research Center of Food Microbiology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Lianzhong Ai
- Shanghai Engineering Research Center of Food Microbiology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Fan Xie
- Shanghai Engineering Research Center of Food Microbiology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
| | - Zhenliang Sun
- Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, 201499 Shanghai, China.
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Virk MS, Virk MA, He Y, Tufail T, Gul M, Qayum A, Rehman A, Rashid A, Ekumah JN, Han X, Wang J, Ren X. The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs. Nutrients 2024; 16:546. [PMID: 38398870 PMCID: PMC10893534 DOI: 10.3390/nu16040546] [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: 01/27/2024] [Revised: 02/10/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024] Open
Abstract
Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.
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Affiliation(s)
- Muhammad Safiullah Virk
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | | | - Yufeng He
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Tabussam Tufail
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
- University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore 54000, Pakistan
| | - Mehak Gul
- Department of Internal Medicine, Sheikh Zayed Hospital, Lahore 54000, Pakistan
| | - Abdul Qayum
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Abdur Rehman
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Arif Rashid
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - John-Nelson Ekumah
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Xu Han
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Junxia Wang
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Xiaofeng Ren
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang 212013, 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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Kleniewska P, Pawliczak R. Alpha-lipoic acid, apocynin or probiotics influence glutathione status and selected inflammatory parameters in C57/BL6 mice when combined with a low-fat diet. Pharmacol Rep 2023; 75:1166-1176. [PMID: 37730940 PMCID: PMC10539412 DOI: 10.1007/s43440-023-00527-8] [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: 05/10/2023] [Revised: 08/18/2023] [Accepted: 08/29/2023] [Indexed: 09/22/2023]
Abstract
BACKGROUND The aim of the study was to determine the potential of a low-fat diet (LFD) to protect against oxidative and inflammatory damage in the course of asthma and obesity when combined with antioxidants (alpha-lipoic acid-ALA, apocynin-APO) or a probiotic (P) (Lactobacillus casei). METHODS The experiments were carried out on ten groups of male C57/BL6 mice that were fed standard fat (SFD), low-fat (LFD), or high-fat (HFD) diets. Ovalbumin (OVA, administered subcutaneously and by inhalation) was used to sensitize the animals. IL-1α, IL-10, eotaxin-1, leptin, and TNF-α concentrations were examined in blood, while total glutathione (GSHt), reduced glutathione (GSH), oxidized glutathione (GSSG) and -SH groups were measured in lung homogenates. RESULTS LFD in combination with the analyzed compounds (APO, P, ALA) significantly decreased the concentration of IL-1α compared to the OVA + HFD group (p < 0.01; p = 0.025; p = 0.002, respectively). Similarly, the treated mice demonstrated lower eotaxin-1 concentrations compared to the HFD group (p < 0.001). Moreover, supplementation of LFD with probiotics significantly increased the concentration of IL-10 vs. controls (p < 0.001) and vs. untreated OVA-sensitized and challenged/obese mice (p < 0.001). Animals administered APO/ALA with LFD displayed a significant decrease in TNF-α concentration compared to OVA + HFD mice (p = 0.013; p = 0.002 respectively). Those treated with ALA displayed significantly improved GSH levels (p = 0.035) compared to OVA + HFD mice. CONCLUSIONS Supplementation of the tested compounds with LFD appears to have a positive influence on the glutathione redox status of pulmonary tissues and selected inflammatory parameters in mouse blood.
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Affiliation(s)
- Paulina Kleniewska
- Department of Immunopathology, Faculty of Medicine, Medical University of Lodz, Żeligowskiego 7/9 (Bldg 2 Rm 177), 90-752, Łódź, Poland.
| | - Rafał Pawliczak
- Department of Immunopathology, Faculty of Medicine, Medical University of Lodz, Żeligowskiego 7/9 (Bldg 2 Rm 177), 90-752, Łódź, Poland
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Lin TY, Zhang YF, Wang Y, Liu Y, Xu J, Liu YL. Nonalcoholic fatty liver disease aggravates acute pancreatitis through bacterial translocation and cholesterol metabolic dysregulation in the liver and pancreas in mice. Hepatobiliary Pancreat Dis Int 2023; 22:504-511. [PMID: 35909061 DOI: 10.1016/j.hbpd.2022.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 07/12/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for severe acute pancreatitis (AP). The underlying mechanism remains unclear. We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice. METHODS C57BL/6N mice were fed on a high-fat diet (HFD) to generate the NAFLD model, and mice in the control group were provided with a normal diet (ND). After being anesthetized with ketamine/xylazine, mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP, and sham operation (SO) was used as control. Serum amylase and Schmidt's pathological score system were used to evaluate AP severity. Bacterial loads, total cholesterol level, and cholesterol metabolic-associated molecules [low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1)] were analyzed in the liver and pancreas. RESULTS Compared with the ND-AP group, mice in the HFD-AP group had severer pancreatitis, manifested with higher serum amylase levels and higher AP pathologic scores, especially the inflammation and hemorrhage scores. Compared with the HFD-SO group and ND-AP group, bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group. Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas, although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group. CONCLUSIONS NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.
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Affiliation(s)
- Tian-Yu Lin
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
| | - Yi-Fan Zhang
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
| | - Yang Wang
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
| | - Yun Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
| | - Jun Xu
- Central Laboratory & Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing 100044, China
| | - Yu-Lan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China.
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Werawatganon D, Vivatvakin S, Somanawat K, Tumwasorn S, Klaikeaw N, Siriviriyakul P, Chayanupatkul M. Effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis. BMC Complement Med Ther 2023; 23:166. [PMID: 37217916 DOI: 10.1186/s12906-023-03998-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 05/14/2023] [Indexed: 05/24/2023] Open
Abstract
BACKGROUND Severe acute pancreatitis is a potentially life-threatening disease. Despite being a common disorder, acute pancreatitis lacks a specific treatment. The present study aimed to examine the effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis. METHODS Male ICR mice were randomly divided into 4 groups (n = 6 per group). The control group received two intraperitoneal (i.p.) injections of normal saline as a vehicle control. The acute pancreatitis (AP) group received two i.p. injections of L-arginine 450 mg/100 g body weight. AP plus probiotics groups received L-arginine to induce acute pancreatitis as above. In the single-strain and mixed-strain groups, mice received 1 mL of Lactobacillus plantarum B7 1 × 108 CFU/mL and 1 mL of Lactobacillus rhamnosus L34 1 × 108 CFU/mL and Lactobacillus paracasei B13 1 × 108 CFU/mL by oral gavage, respectively for 6 days starting 3 days prior to the AP induction. All mice were sacrificed 72 h after L-arginine injection. Pancreatic tissue was obtained for histological evaluation and immunohistochemical studies for myeloperoxidase, whereas ileal tissue was used for immunohistochemical studies for occludin, and claudin-1. Blood samples were collected for amylase analysis. RESULTS Serum amylase levels and pancreatic myeloperoxidase levels in the AP group were significantly higher than in controls and significantly decreased in probiotic groups compared with the AP group. Ileal occludin and claudin-1 levels were significantly lower in the AP group than in controls. Ileal occludin levels significantly increased, whereas ileal claudin-1 levels did not significantly change in both probiotic groups as compared with the AP group. The pancreatic histopathology showed significantly higher degree of inflammation, edema, and fat necrosis in the AP group, and these changes improved in mixed-strained probiotic groups. CONCLUSIONS Probiotics, particularly the mixed-strain ones, attenuated AP via the reduction of inflammation and the maintenance of intestinal integrity.
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Affiliation(s)
- Duangporn Werawatganon
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sarocha Vivatvakin
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kanjana Somanawat
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Somying Tumwasorn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Naruemon Klaikeaw
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Prasong Siriviriyakul
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Maneerat Chayanupatkul
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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10
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Gopi S, Saraya A, Gunjan D. Nutrition in acute pancreatitis. World J Gastrointest Surg 2023; 15:534-543. [PMID: 37206070 PMCID: PMC10190733 DOI: 10.4240/wjgs.v15.i4.534] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/10/2023] [Accepted: 03/21/2023] [Indexed: 04/22/2023] Open
Abstract
Acute pancreatitis (AP) has varying severity, and moderately severe and severe AP has prolonged hospitalization and requires multiple interventions. These patients are at risk of malnutrition. There is no proven pharmacotherapy for AP, however, apart from fluid resuscitation, analgesics, and organ support, nutrition plays an important role in the management of AP. Oral or enteral nutrition (EN) is the preferred route of nutrition in AP, however, in a subset of patients, parenteral nutrition is required. EN has various physiological benefits and decreases the risk of infection, intervention, and mortality. There is no proven role of probiotics, glutamine supplementation, antioxidants, and pancreatic enzyme replacement therapy in patients with AP.
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Affiliation(s)
- Srikanth Gopi
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Anoop Saraya
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Deepak Gunjan
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, India
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11
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Temel HY, Kaymak Ö, Kaplan S, Bahcivanci B, Gkoutos GV, Acharjee A. Role of microbiota and microbiota-derived short-chain fatty acids in PDAC. Cancer Med 2023; 12:5661-5675. [PMID: 36205023 PMCID: PMC10028056 DOI: 10.1002/cam4.5323] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 09/08/2022] [Accepted: 09/23/2022] [Indexed: 02/05/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive lethal diseases among other cancer types. Gut microbiome and its metabolic regulation play a crucial role in PDAC. Metabolic regulation in the gut is a complex process that involves microbiome and microbiome-derived short-chain fatty acids (SCFAs). SCFAs regulate inflammation, as well as lipid and glucose metabolism, through different pathways. This review aims to summarize recent developments in PDAC in the context of gut and oral microbiota and their associations with short-chain fatty acid (SCFA). In addition to this, we discuss possible therapeutic applications using microbiota in PDAC.
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Affiliation(s)
- Hülya Yılmaz Temel
- Department of Bioengineering, Faculty of EngineeringEge UniversityIzmirTurkey
| | - Öznur Kaymak
- Department of Bioengineering, Faculty of EngineeringEge UniversityIzmirTurkey
| | - Seren Kaplan
- Department of Bioengineering, Faculty of EngineeringEge UniversityIzmirTurkey
| | - Basak Bahcivanci
- Institute of Cancer and Genomic Sciences, University of BirminghamBirminghamUK
| | - Georgios V. Gkoutos
- Institute of Cancer and Genomic Sciences, University of BirminghamBirminghamUK
- National Institute for Health Research Surgical Reconstruction, Queen Elizabeth Hospital BirminghamBirminghamUK
- MRC Health Data Research UK (HDR UK)BirminghamUK
| | - Animesh Acharjee
- Institute of Cancer and Genomic Sciences, University of BirminghamBirminghamUK
- National Institute for Health Research Surgical Reconstruction, Queen Elizabeth Hospital BirminghamBirminghamUK
- MRC Health Data Research UK (HDR UK)BirminghamUK
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12
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Guidetti C, Salvini E, Viri M, Deidda F, Amoruso A, Visciglia A, Drago L, Calgaro M, Vitulo N, Pane M, Caucino AC. Randomized Double-Blind Crossover Study for Evaluating a Probiotic Mixture on Gastrointestinal and Behavioral Symptoms of Autistic Children. J Clin Med 2022; 11:jcm11185263. [PMID: 36142909 PMCID: PMC9504504 DOI: 10.3390/jcm11185263] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/24/2022] [Accepted: 08/29/2022] [Indexed: 11/26/2022] Open
Abstract
Autism spectrum disorders (ASDs) represent a diagnostic challenge with a still partially uncertain etiology, in which genetic and environmental factors have now been assessed. Among the hypotheses underlying the involvement of biological and environmental factors, the gut–brain axis is of particular interest in autism spectrum disorders. Several studies have highlighted the related incidence of particular gastrointestinal symptoms (GISs) in children suffering from ASDs. Probiotics have shown success in treating several gastrointestinal dysbiotic disorders; therefore, it is plausible to investigate whether they can alleviate behavioral symptoms as well. On these bases, a randomized double-blind crossover study with a placebo was conducted, evaluating the effects of a mixture of probiotics in a group of 61 subjects aged between 24 months and 16 years old with a diagnosis of ASD. Behavioral evaluation was performed through the administration of a questionnaire including a Parenting Stress Index (PSI) test and the Vineland Adaptive Behavior Scale (VABS). The Psycho-Educational Profile and the Autism Spectrum Rating Scale (ASRS) were also evaluated. Microbial composition analyses of fecal samples of the two groups was also performed. The study showed significant improvements in GISs, communication skills, maladaptive behaviors, and perceived parental stress level after the administration of probiotics. Microbiome alpha diversity was comparable between treatment arms and no significant differences were found, although beta diversity results were significantly different in the treatment group between T0 and T1 time points. Streptococcus thermophilus, Bifidobacterium longum, Limosilactobacillus fermentum, and Ligilactobacillus salivarius species were identified as some of the most discriminant taxa positively associated with T1 samples. This preliminary study corroborates the relationship between intestinal microbiota and ASD recently described in the literature.
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Affiliation(s)
- Cristina Guidetti
- Department of Child Neuropsychiatry, University Hospital Maggiore della Carità, 28100 Novara, Italy
| | - Elena Salvini
- Department of Child Neuropsychiatry, University Hospital Maggiore della Carità, 28100 Novara, Italy
| | - Maurizio Viri
- Department of Child Neuropsychiatry, University Hospital Maggiore della Carità, 28100 Novara, Italy
| | | | - Angela Amoruso
- Probiotical Research Srl, Via E. Mattei 3, 28100 Novara, Italy
| | | | - Lorenzo Drago
- Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
- Correspondence:
| | - Matteo Calgaro
- Department of Biotechnology, University of Verona, 37100 Verona, Italy
| | - Nicola Vitulo
- Department of Biotechnology, University of Verona, 37100 Verona, Italy
| | - Marco Pane
- Probiotical Research Srl, Via E. Mattei 3, 28100 Novara, Italy
| | - Anna Claudia Caucino
- Department of Child Neuropsychiatry, University Hospital Maggiore della Carità, 28100 Novara, Italy
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13
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Jiang Z, Li M, McClements DJ, Liu X, Liu F. Recent advances in the design and fabrication of probiotic delivery systems to target intestinal inflammation. Food Hydrocoll 2022. [DOI: 10.1016/j.foodhyd.2021.107438] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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14
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Zhang T, Gao G, Sakandar HA, Kwok LY, Sun Z. Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target. Front Nutr 2022; 9:814269. [PMID: 35242797 PMCID: PMC8885515 DOI: 10.3389/fnut.2022.814269] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/21/2022] [Indexed: 12/12/2022] Open
Abstract
Pancreatic-related disorders such as pancreatitis, pancreatic cancer, and type 1 diabetes mellitus (T1DM) impose a substantial challenge to human health and wellbeing. Even though our understanding of the initiation and progression of pancreatic diseases has broadened over time, no effective therapeutics is yet available for these disorders. Mounting evidence suggests that gut dysbiosis is closely related to human health and disease, and pancreatic diseases are no exception. Now much effort is under way to explore the correlation and eventually potential causation between the gut microbiome and the course of pancreatic diseases, as well as to develop novel preventive and/or therapeutic strategies of targeted microbiome modulation by probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) for these multifactorial disorders. Attempts to dissect the intestinal microbial landscape and its metabolic profile might enable deep insight into a holistic picture of these complex conditions. This article aims to review the subtle yet intimate nexus loop between the gut microbiome and pancreatic diseases, with a particular focus on current evidence supporting the feasibility of preventing and controlling pancreatic diseases via microbiome-based therapeutics and therapies.
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Affiliation(s)
- Tao Zhang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Guangqi Gao
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Hafiz Arbab Sakandar
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Lai-Yu Kwok
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Zhihong Sun
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
- *Correspondence: Zhihong Sun
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15
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Abstract
Coronavirus disease 2019 (COVID-19) is the leading pandemic facing the world in 2019/2020; it is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which necessitates clear understanding of the infectious agent. The virus manifests aggressive behavior with severe clinical presentation and high mortality rate, especially among the elderly and patients living with chronic diseases. In the recent years, the role of gut microbiota, in health and disease, has been progressively studied and highlighted. It is through gut microbiota-organ bidirectional pathways, such as gut-brain axis, gut-liver axis, and gut-lung axis, that the role of gut microbiota in prompting lung disease, among other diseases, has been proposed and accepted. It is also known that respiratory viral infections, such as COVID-19, induce alterations in the gut microbiota, which can influence immunity. Based on the fact that gut microbiota diversity is decreased in old age and in patients with certain chronic diseases, which constitute two of the primary fatality groups in COVID-19 infections, it can be assumed that the gut microbiota may play a role in COVID-19 pathology and fatality rate. Improving gut microbiota diversity through personalized nutrition and supplementation with prebiotics/probiotics will mend the immunity of the body and hence could be one of the prophylactic strategies by which the impact of COVID-19 can be minimized in the elderly and immunocompromised patients. In this chapter, the role of dysbiosis in COVID-19 will be clarified and the possibility of using co-supplementation of personalized prebiotics/probiotics with current therapies will be discussed.
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16
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Zhou J, Sun S, Luan S, Xiao X, Yang Y, Mao C, Chen L, Zeng X, Zhang Y, Yuan Y. Gut Microbiota for Esophageal Cancer: Role in Carcinogenesis and Clinical Implications. Front Oncol 2021; 11:717242. [PMID: 34733778 PMCID: PMC8558403 DOI: 10.3389/fonc.2021.717242] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 09/24/2021] [Indexed: 02/05/2023] Open
Abstract
Esophageal cancer (EC) is a common malignant tumor of the upper digestive tract. The microbiota in the digestive tract epithelium comprises a large number of microorganisms that adapt to the immune defense and interact with the host to form symbiotic networks, which affect many physiological processes such as metabolism, tissue development, and immune response. Reports indicate that there are microbial compositional changes in patients with EC, which provides an important opportunity to advance clinical applications based on findings on the gut microbiota. For example, microbiota detection can be used as a biomarker for screening and prognosis, and microorganism levels can be adjusted to treat cancer and decrease the adverse effects of treatment. This review aims to provide an outline of the gut microbiota in esophageal neoplasia, including the mechanisms involved in microbiota-related carcinogenesis and the prospect of utilizing the microbiota as EC biomarkers and treatment targets. These findings have important implications for translating the use of gut microbiota in clinical applications.
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Affiliation(s)
- Jianfeng Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Shangwei Sun
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Luan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yushang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chengyi Mao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Longqi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yonggang Zhang
- Department of Periodical Press, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.,Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Yuan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
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17
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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: 17] [Impact Index Per Article: 4.3] [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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18
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Abdul Rahman R, Lamarca A, Hubner RA, Valle JW, McNamara MG. The Microbiome as a Potential Target for Therapeutic Manipulation in Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13153779. [PMID: 34359684 PMCID: PMC8345056 DOI: 10.3390/cancers13153779] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Pancreatic cancer is one of the most lethal cancers. It is a difficult cancer to treat, and the complexity surrounding the pancreatic tumour is one of the contributing factors. The microbiome is the collection of microorganisms within an environment and its genetic material. They reside on body surfaces and most abundantly within the human gut in symbiotic balance with their human host. Disturbance in the balance can lead to many diseases, including cancers. Significant advances have been made in cancer treatment since the introduction of immunotherapy, and the microbiome may play a part in the outcome and survival of patients with cancer, especially those treated with immunotherapy. Immunotherapy use in pancreatic cancer remains challenging. This review will focus on the potential interaction of the microbiome with pancreas cancer and how this could be manipulated. Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.
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Affiliation(s)
- Rozana Abdul Rahman
- Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; (A.L.); (R.A.H.)
| | - Richard A. Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; (A.L.); (R.A.H.)
| | - Juan W. Valle
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Mairéad G. McNamara
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
- Correspondence:
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19
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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: 29] [Impact Index Per Article: 7.3] [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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20
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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: 32] [Impact Index Per Article: 8.0] [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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21
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Abstract
Background: Pneumonia, as a fairly prevalent illness, is the main cause of hospital mortality. The major cause of mortality and morbidity of pneumonia is due to bacteria. The presence of multi-drug resistant pathogens and no response to treatment have aroused considerable interest in the use of probiotic components to prevent infections. Objectives: Given that few studies have evaluated the efficacy of probiotics in reducing bacterial pneumonia, the current aimed to evaluate the role of probiotics in decreasing pneumonia. Methods: This double-blind, randomized clinical trial study was conducted on 100 patients diagnosed with bacterial pneumonia in Shahid Beheshti Hospital, Kashan, Iran, during 2018. Patients were randomly classified into two groups (n = 50). One group (case) received two sachets of probiotic/daily for five days, and another group (control) received placebo. Moreover, patients in both groups received the same treatment protocol. All data were extracted from medical records. Chi-square test and independent t-test were used for analysis of data. P < 0.05 was considered statistically significant. Results: No significant difference was seen between case and control groups regarding age, gender, and duration of symptoms before hospitalization (P > 0.05), which implies a completely random classification of two groups. The mean duration of hospitalization, dyspnea, tachypnea, cough, fever, and crackles was significantly decreased in the case group compared to the control group (P < 0.05). Conclusion: The use of probiotics can be effective in reducing the duration of dyspnea, tachypnea, cough, fever, and length of hospitalization. Therefore, probiotics may be considered a promising treatment for the development of new anti-infectious therapy. In addition, the usage of probiotics along with antibiotics is suggested for decreasing pneumonia complications and improving the efficacy of therapy.
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22
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Lakananurak N, Gramlich L. Nutrition management in acute pancreatitis: Clinical practice consideration. World J Clin Cases 2020; 8:1561-1573. [PMID: 32432134 PMCID: PMC7211526 DOI: 10.12998/wjcc.v8.i9.1561] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 03/07/2020] [Accepted: 04/21/2020] [Indexed: 02/05/2023] Open
Abstract
Acute pancreatitis (AP) is a common gastrointestinal disease and the leading cause of hospital admission and healthcare burden among gastrointestinal disorders in many countries. Patients can present with varying degrees of inflammation and disease severity, ranging from self-limiting mild AP to devastating and fatal severe AP. Many factors contribute to malnutrition in AP, especially abnormal metabolism and catabolism related to inflammation. The concept of "pancreatic rest" is not evidence-based. There is however, emerging evidence that supports the use of oral or enteral nutrition to improve nutrition status and to reduce local and systemic inflammation, complications, and death. In mild disease, patients are generally able to initiate solid oral diet and do not require specialized nutrition care such as enteral or parenteral nutrition. In contrast, nutrition interventions are imperative in moderately severe and severe AP. The current article aims to review the latest evidence and suggest practical nutrition interventions in patients with AP, including nutrition requirements, routes of nutrition treatment, types of formula, and the role of nutritional supplements, such as glutamine, probiotics, omega-3 fatty acids, and antioxidants.
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Affiliation(s)
- Narisorn Lakananurak
- Department of Medicine, University of Alberta, Edmonton T6G 2R3, Alberta, Canada
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Leah Gramlich
- Department of Medicine, University of Alberta, Edmonton T6G 2R3, Alberta, Canada
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23
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Cen ME, Wang F, Su Y, Zhang WJ, Sun B, Wang G. Gastrointestinal microecology: a crucial and potential target in acute pancreatitis. Apoptosis 2019; 23:377-387. [PMID: 29926313 DOI: 10.1007/s10495-018-1464-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In the early stage of acute pancreatitis (AP), abundant cytokines induced by local pancreatic inflammation enter the bloodstream, further cause systemic inflammatory response syndrome (SIRS) by "trigger effect", which eventually leads to multiple organ dysfunction syndrome (MODS). During SIRS and MODS, the intestinal barrier function was seriously damaged accompanied by the occurrence of gut-derived infection which forms a "second hit summit" by inflammatory overabundance. Gastrointestinal microecology, namely the biologic barrier, could be transformed into a pathogenic state, which is called microflora dysbiosis when interfered by the inflammatory stress during AP. More and more evidences indicate that gastrointestinal microflora dysbiosis plays a key role in "the second hit" induced by AP gut-derived infection. Therefore, the maintenance of gastrointestinal microecology balance is likely to provide an effective method in modulating systemic infection of AP. This article reviewed the progress of gastrointestinal microecology in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.
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Affiliation(s)
- Meng-Er Cen
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.,Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Nephropathy, Hangzhou, Zhejiang, China
| | - Feng Wang
- Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ying Su
- Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Wang-Jun Zhang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China
| | - Gang Wang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.
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24
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Li A, Wang Y, Pei L, Mehmood K, Li K, Qamar H, Iqbal M, Waqas M, Liu J, Li J. Influence of dietary supplementation with Bacillus velezensis on intestinal microbial diversity of mice. Microb Pathog 2019; 136:103671. [PMID: 31437575 DOI: 10.1016/j.micpath.2019.103671] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/11/2019] [Accepted: 08/19/2019] [Indexed: 12/13/2022]
Abstract
Yaks are an aboriginal breed of the Qinghai-Tibet plateau (3000 m), which are highly adaptable to cold and hypoxic environments. It is noticed that hypoxia and hypothermia can induce changes in intestinal microbial structure in animals. Increasing evidences suggested that probiotics supplementation can improve the balance of gut microbiota of animals. However, so far, very few studies have emphasized on the probiotics isolated from yaks in the Qinghai-Tibet Plateau. Therefore, a potential probiotic strain Bacillus velezensis was isolated from yaks. In the present study, a total of 18 Kunming mice (15-18 g) were equally distributed into two groups; control and probiotic treated groups (1 × 109 CFU/day). During the experimental period, all the mice from both groups were given standard normal diet ad libitum. At the end of the experiment, mice were euthanized and the intestines (duodenum, jejunum, ileum, and cecum) were removed for high-throughput sequencing. The results demonstrated that Bacillus velezensis supplementation showed beneficial effects on the gut microbiota of mice. Specifically, Bacillus velezensis supplementation increased the population of Lactobacillus and Ruminococcus in the duodenum, and Candidatus Arthromitus in the jejunum. Additionally, Acinetobacter in the duodenum and Helicobacter in the cecum were decreased after feeding Bacillus velezensis. Altogether, these findings suggested that Bacillus velezensis isolated from Tibetan yaks can improve gut microbiota of mice.
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Affiliation(s)
- Aoyun Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Yaping Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Lulu Pei
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Khalid Mehmood
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China; University College of Veterinary & Animal Sciences, The Islamia University of Bahawalpur, 63100, Pakistan
| | - Kun Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Hammad Qamar
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Mudassar Iqbal
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China; University College of Veterinary & Animal Sciences, The Islamia University of Bahawalpur, 63100, Pakistan
| | - Muhammad Waqas
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Juanjuan Liu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Jiakui Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China; College of Animals Husbandry and Veterinary Medicine, Tibet Agricultural and Animal Husbandry University, Linzhi, Tibet, 860000, PR China.
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25
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Russell JT, Roesch LFW, Ördberg M, Ilonen J, Atkinson MA, Schatz DA, Triplett EW, Ludvigsson J. Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome. Nat Commun 2019; 10:3621. [PMID: 31399563 PMCID: PMC6689114 DOI: 10.1038/s41467-019-11460-x] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 07/11/2019] [Indexed: 12/20/2022] Open
Abstract
Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations. These genes remain by far the greatest risk factors in the development of type 1 diabetes and celiac disease. Despite this, little is known about HLA influences on the composition of the human gut microbiome, a potential source of environmental influence on disease. Here, using a general population cohort from the All Babies in Southeast Sweden study, we report that genetic risk for developing type 1 diabetes autoimmunity is associated with distinct changes in the gut microbiome. Both the core microbiome and beta diversity differ with HLA risk group and genotype. In addition, protective HLA haplotypes are associated with bacterial genera Intestinibacter and Romboutsia. Thus, general population cohorts are valuable in identifying potential environmental triggers or protective factors for autoimmune diseases that may otherwise be masked by strong genetic control.
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Affiliation(s)
- Jordan T Russell
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences University of Florida, Gainesville, 32611-0700, FL, USA
| | - Luiz F W Roesch
- Biological Sciences, Universidade Federal do Pampa, São Gabriel, 97300-000, Brazil
| | - Malin Ördberg
- Crown Princess Victoria's Children's Hospital, Region Östergötland, Division of Pediatrics, Linköping University, Linköping, SE 58185, Sweden
| | - Jorma Ilonen
- Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, and Clinical Microbiology, Turku University Hospital, Turku, 20521, Finland
| | - Mark A Atkinson
- Department of Pathology, University of Florida Diabetes Institute, Gainesville, 32610, FL, USA
- Department of Pediatrics, College of Medicine, University of Florida, Gainesville, 32610, FL, USA
| | - Desmond A Schatz
- Department of Pediatrics, College of Medicine, University of Florida, Gainesville, 32610, FL, USA
| | - Eric W Triplett
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences University of Florida, Gainesville, 32611-0700, FL, USA.
| | - Johnny Ludvigsson
- Crown Princess Victoria's Children's Hospital, Region Östergötland, Division of Pediatrics, Linköping University, Linköping, SE 58185, Sweden
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26
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Pan LL, Niu W, Fang X, Liang W, Li H, Chen W, Zhang H, Bhatia M, Sun J. Clostridium butyricum Strains Suppress Experimental Acute Pancreatitis by Maintaining Intestinal Homeostasis. Mol Nutr Food Res 2019; 63:e1801419. [PMID: 31034143 DOI: 10.1002/mnfr.201801419] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 04/13/2019] [Indexed: 01/24/2023]
Abstract
SCOPE Acute pancreatitis (AP) is a common abdominal inflammatory disease. Disturbed gut homeostasis secondary to pancreatic inflammation aggravates the condition retroactively. The current study investigates potential beneficial effects of Clostridium butyricum (C. butyricum) strains on AP and underlying mechanisms. METHODS AND RESULTS C. butyricum strains MIYAIRI 588 (CBM588) and CGMCC0313.1 (CB0313.1) were supplemented to mice for three weeks before experimental AP or SAP induction. Both CBM588 and CB0313.1 protected against AP, as evidenced by reduced serum amylase and lipase levels, pancreatic edema, and myeloperoxidase activity. Amelioration of both experimental AP and SAP by CB0313.1 indicated a non-model-specific effect. Moreover, C. butyricum inhibited pancreatic neutrophil and dendritic cell infiltration, nucleotide-binding domain leucine-rich repeat-containing family, pyrin domain-containing 3 inflammasome activation, and pro-inflammatory pathways. Additionally in the gut, C. butyricum strains attenuated AP-associated intestinal inflammation and barrier dysfunction, accompanied with reduced pathogenic bacteria Escherichia coli and Enterococcus penetration into pancreas. Gut microbiome analyses further revealed that beneficial effects of C. butyricum on pancreatic-gut homeostasis were correlated with improved dysbiosis. In particular, relative abundance of Desulfovibrionaceae decreased, and Verrucomicrobiaceae Clostridiaceae and Lactobacillaceae increased. CONCLUSIONS For the first time, a protective effect of C. butyricum in AP by modulating intestinal homeostasis is demonstrated.
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Affiliation(s)
- Li-Long Pan
- School of Medicine, Jiangnan University, Wuxi, 214122, P. R. China
| | - Wenying Niu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Xin Fang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Wenjie Liang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Hongli Li
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Madhav Bhatia
- Inflammation Research Group, Department of Pathology, University of Otago, Christchurch, 8140, New Zealand
| | - Jia Sun
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
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27
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van den Nieuwboer M, Claassen E. Dealing with the remaining controversies of probiotic safety. Benef Microbes 2019; 10:605-616. [PMID: 31131618 DOI: 10.3920/bm2018.0159] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
A clear safety profile of probiotics in clinical practice is essential in decision-making for all stakeholders and regulators. Probiotics have been investigated in different target populations, conditions and age groups. This also includes the use of probiotics in critically ill patients. Despite promising results reported with the use of probiotics and synbiotics, there is still a lively discussion regarding the proper and safe use of probiotics among physicians, researchers and regulators. This doubt and debate was sparked by the high incidence in mortality reported in a study with critically ill patients. Whereas no causal relationship has been established since, safety of probiotic has been questioned. In response, an overwhelming body of evidence suggesting that probiotics are safe has been compiled. Moreover, data indicates that probiotics reduce the number of adverse events compared to the control. However, due to a lack of standardised safety reporting in clinical studies, a strong evidence base on probiotic safety remains to be established. Here, we will discuss: (1) the rationale for using probiotics in the critically ill; (2) what happened during the Dutch Pancreatitis trial; (3) what are the known safety risks of probiotics based on the available data; and finally (4) how standardisation in safety reporting can drive probiotic innovation. Building a strong safety profile for probiotic strains will solidify its use in individuals that can benefit the most from microbial modulation.
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Affiliation(s)
- M van den Nieuwboer
- Athena Institute, VU Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, the Netherlands
| | - E Claassen
- Athena Institute, VU Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, the Netherlands
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28
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Silva JCP, Mota M, Martins FO, Nogueira C, Gonçalves T, Carneiro T, Pinto J, Duarte D, Barros AS, Jones JG, Gil AM. Intestinal Microbial and Metabolic Profiling of Mice Fed with High-Glucose and High-Fructose Diets. J Proteome Res 2018; 17:2880-2891. [PMID: 29923728 DOI: 10.1021/acs.jproteome.8b00354] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease; however, the mechanisms through which glucose and fructose promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with diets with glucose (G) or fructose (F) as sole carbohydrates, and a third group was fed with a normal chow carbohydrate mixture (N). Fecal metabolites were profiled by nuclear magnetic resonance (NMR) and microbial composition by real-time polymerase chain reaction (qPCR). Although N, G and F mice exhibited similar weight gains (with slight slower gains for F) and glucose tolerance, multivariate analysis of NMR data indicated that F mice were separated from N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine, and xylose. The different sugar diets also resulted in distinct intestinal microbiota profiles. That associated with fructose seemed to hold more potential to induce host metabolic disturbances compared to glucose, mainly by promoting bile acid deconjugation and taurine release and compromising intestinal barrier integrity. This may reflect the noted nonquantitative intestinal fructose absorption hence increasing its availability for microbial metabolism, a subject for further investigation.
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Affiliation(s)
- João C P Silva
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal
| | - Marta Mota
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,Institute of Microbiology, Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Fátima O Martins
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,CEDOC, NOVA Medical School , Universidade NOVA de Lisboa , Rua Câmara Pestana, n°6, 6A, edifício II, piso 3 , 1150-082 Lisbon , Portugal
| | - Célia Nogueira
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,Institute of Microbiology, Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Teresa Gonçalves
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,Institute of Microbiology, Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Tatiana Carneiro
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
| | - Joana Pinto
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal.,UCIBIO@REQUIMTE/Toxicological Laboratory, Biological Science Department, Faculty of Pharmacy , University of Porto , 4050-313 Porto , Portugal
| | - Daniela Duarte
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
| | - António S Barros
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal.,Department of Cardiothoracic Surgery and Physiology, Faculty of Medicine , University of Porto , 4200-319 , Porto , Portugal
| | - John G Jones
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,CEDOC, NOVA Medical School , Universidade NOVA de Lisboa , Rua Câmara Pestana, n°6, 6A, edifício II, piso 3 , 1150-082 Lisbon , Portugal.,APDP - Portuguese Diabetes Association , Lisbon , Portugal
| | - Ana M Gil
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
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29
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Tian X, Pi YP, Liu XL, Chen H, Chen WQ. Supplemented Use of Pre-, Pro-, and Synbiotics in Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis of 13 Randomized Controlled Trials. Front Pharmacol 2018; 9:690. [PMID: 30002627 PMCID: PMC6031870 DOI: 10.3389/fphar.2018.00690] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Accepted: 06/07/2018] [Indexed: 01/30/2023] Open
Abstract
Introduction: The role of pre-, pro-, and synbiotics supplemented to standard enteral nutrition in severe acute pancreatitis (SAP) remains unclear. We performed this updated meta-analysis to determine the value of pre-, pro- and synbiotics supplemented to standard enteral nutrition in predicted SAP. Methods: A systematic search in PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Eligible studies were randomized controlled trials (RCTs) that compared the effects of pre-, pro-, and synbiotics supplemented to standard enteral nutrition with control regime in predicted SAP patients. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (95% CI) were used to express the estimates of dichotomous and continuous data respectively. Results: 13 RCTs comprising an aggregate total of 950 patients were eventually enrolled. Pooled results suggested that supplemented use of pre-, pro- and synbiotics effectively shorten the length of hospital stay in Chinese SAP cohorts (6 RCTs, MD = −5.57, 95% CI = −8.21 to −2.93, P < 0.001); however significant differences with regard to remaining clinical outcomes were not detected for all patients. Further analysis based on category of interventions including pre-, pro- and synbiotics also confirmed the findings to be reliable. Conclusions: Supplemented use of pre-, pro and synbiotics reduced the length of hospital stay in Chinese SAP cohorts. And thus, we concluded that pre-, pro- and synbiotics supplemented to standard enteral nutrition may be a potential option for the treatment of SAP patients. However, we also suggest designing further studies with large-scale and rigorous methods of addressing data to establish the effects and safety of supplemented use of pre-, pro- and synbiotics for SAP patients due to the presence of limitations.
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Affiliation(s)
- Xu Tian
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Hospital & Chongqing Cancer Institute, Chongqing, China.,Editorial Office, TMR Integrative Nursing, TMR Publishing Group, Tianjin, China
| | - Yuan-Ping Pi
- Department of Nursing, Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital & Chongqing Cancer Hospital & Chongqing Cancer Institute, Chongqing, China
| | - Xiao-Ling Liu
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Hospital & Chongqing Cancer Institute, Chongqing, China
| | - Hui Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Hospital & Chongqing Cancer Institute, Chongqing, China
| | - Wei-Qing Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Hospital & Chongqing Cancer Institute, Chongqing, China
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30
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Zhang M, Zhu HM, He F, Li BY, Li XC. Association between acute pancreatitis and small intestinal bacterial overgrowth assessed by hydrogen breath test. World J Gastroenterol 2017; 23:8591-8596. [PMID: 29358867 PMCID: PMC5752719 DOI: 10.3748/wjg.v23.i48.8591] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 12/12/2017] [Accepted: 12/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To elucidate the effects of small intestinal bacterial overgrowth (SIBO) on the severity and complications of acute pancreatitis (AP). METHODS In total, 208 patients with AP as defined by the revised Atlanta classification were admitted to Xuanwu Hospital of Capital Medical University from 2013 to 2016. All patients were admitted within 72 h of AP onset. The hydrogen breath test was performed 7 d after AP onset to detect hydrogen production and evaluate the development of SIBO. The incidence of SIBO was analyzed in patients with AP of three different severity grades. The association between SIBO and complications of AP was also assessed. RESULTS Of the 27 patients with severe AP (SAP), seven (25.92%) developed SIBO. Of the 86 patients with moderately severe AP (MSAP), 22 (25.58%) developed SIBO. Of the 95 patients with mild AP (MAP), eight (8.42%) developed SIBO. There were significant differences in the rates of SIBO among patients with AP of different severities. Additionally, more severe AP was associated with higher rates of SIBO positivity (P < 0.05). SIBO in patients with AP mainly occurred within 72 h of the onset of AP. The incidence of organ failure was significantly higher in patients with SIBO than in those without (P < 0.05). CONCLUSION SIBO occurs more frequently in patients with MSAP or SAP than in those with MAP, usually ≤ 72 h after AP onset. Additionally, SIBO is associated with organ failure.
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Affiliation(s)
- Mei Zhang
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Hong-Ming Zhu
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Fang He
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Bang-Yi Li
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Xiao-Cui Li
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
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31
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El Hage R, Hernandez-Sanabria E, Van de Wiele T. Emerging Trends in "Smart Probiotics": Functional Consideration for the Development of Novel Health and Industrial Applications. Front Microbiol 2017; 8:1889. [PMID: 29033923 PMCID: PMC5626839 DOI: 10.3389/fmicb.2017.01889] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 09/14/2017] [Indexed: 12/12/2022] Open
Abstract
The link between gut microbiota and human health is well-recognized and described. This ultimate impact on the host has contributed to explain the mutual dependence between humans and their gut bacteria. Gut microbiota can be manipulated through passive or active strategies. The former includes diet, lifestyle, and environment, while the latter comprise antibiotics, pre- and probiotics. Historically, conventional probiotic strategies included a phylogenetically limited diversity of bacteria and some yeast strains. However, biotherapeutic strategies evolved in the last years with the advent of fecal microbiota transplant (FMT), successfully applied for treating CDI, IBD, and other diseases. Despite the positive outcomes, long-term effects resulting from the uncharacterized nature of FMT are not sufficiently studied. Thus, developing strategies to simulate the FMT, using characterized gut colonizers with identified phylogenetic diversity, may be a promising alternative. As the definition of probiotics states that the microorganism should have beneficial effects on the host, several bacterial species with proven efficacy have been considered next generation probiotics. Non-conventional candidate strains include Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, and members of the Clostridia clusters IV, XIVa, and XVIII. However, viable intestinal delivery is one of the current challenges, due to their stringent survival conditions. In this review, we will cover current perspectives on the development and assessment of next generation probiotics and the approaches that industry and stakeholders must consider for a successful outcome.
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Affiliation(s)
| | | | - Tom Van de Wiele
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
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32
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Guo SH, Wang HF, Nian ZG, Wang YD, Zeng QY, Zhang G. Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract. Sci Rep 2017; 7:10566. [PMID: 28874771 PMCID: PMC5585165 DOI: 10.1038/s41598-017-11127-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 08/18/2017] [Indexed: 12/19/2022] Open
Abstract
Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.
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Affiliation(s)
- Song-He Guo
- Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Hai-Fang Wang
- Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Zhi-Gang Nian
- Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Yi-Dan Wang
- Department of School of Life Science, Sun Yat-sen University, Guangzhou, China
| | - Qiu-Yao Zeng
- Department of Clinical Laboratory Medicine, Sun Yat-sen University cancer center, Guangzhou, China, Guangzhou, China
| | - Ge Zhang
- Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
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Jiang Z, Liang H, Huang Z, Tang J, Tang L. Sham Feeding with Chewing Gum in Early Stage of Acute Pancreatitis: A Randomized Clinical Trial. Med Sci Monit 2017; 23:623-630. [PMID: 28154369 PMCID: PMC5304949 DOI: 10.12659/msm.903132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background The correlation between sham feeding and acute pancreatitis (AP) has only been examined in limited studies. We aimed to investigate the efficacy and safety of sham feeding in the early stage of AP. Material/Methods A randomized controlled clinical trial was performed. Equal groups of AP patients were recruited. Patients in the sham feeding group received chewing gum 4 times a day after admission. All patients in the trial received standard treatment consistent with the guidelines for AP. The primary outcomes were mortality, length of stay (LOS), and medical expenses. Secondary outcomes were the incidence of complications and other adverse events, return of gastrointestinal function, the details of enteral nutrition and intra-abdominal pressure. Results From May 2014 to December 2015, a total of 204 patients were recruited. The LOS and hospital costs in the sham feeding group were reduced, although mortality was equivalent between groups. The return of gastrointestinal function occurred earlier in the sham feeding group, with no complications related to gum chewing. Conclusions Sham feeding with chewing gum is safe and efficacious in the early stage of AP.
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Affiliation(s)
- Zongxing Jiang
- Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan, China (mainland)
| | - Hongyin Liang
- Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan, China (mainland)
| | - Zhu Huang
- Postgraduate Department, Third Military Medical University, Chongqing, China (mainland)
| | - Jiajia Tang
- Department of Medical Imaging, Chongqing Medical University, Chongqing, China (mainland)
| | - Lijun Tang
- Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan, China (mainland)
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The Influence of Probiotic Lactobacillus casei in Combination with Prebiotic Inulin on the Antioxidant Capacity of Human Plasma. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:1340903. [PMID: 27066188 PMCID: PMC4808675 DOI: 10.1155/2016/1340903] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 02/05/2016] [Accepted: 02/11/2016] [Indexed: 02/07/2023]
Abstract
The aim of the present study was to assess whether probiotic bacteria Lactobacillus casei (4 × 108 CFU) influences the antioxidant properties of human plasma when combined with prebiotic Inulin (400 mg). Experiments were carried out on healthy volunteers (n = 32). Volunteers were divided according to sex (16 male and 16 female) and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 weeks, at the end of the study. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, and the ferric reducing ability of plasma (FRAP) in human plasma were examined. The administration of synbiotics containing L. casei plus Inulin resulted in a significant increase in FRAP values (p = 0.00008) and CAT activity (p = 0.02) and an insignificant increase in SOD and GPx activity compared to controls. Synbiotics containing L. casei (4 × 108 CFU) with prebiotic Inulin (400 mg) may have a positive influence on human plasma antioxidant capacity and the activity of selected antioxidant enzymes.
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Şenocak R, Yigit T, Kılbaş Z, Coşkun AK, Harlak A, Menteş MÖ, Kılıç A, Günal A, Kozak O. The Effects of Total Colectomy on Bacterial Translocation in a Model of Acute Pancreatitis. Indian J Surg 2015; 77:412-418. [PMID: 26730036 PMCID: PMC4692848 DOI: 10.1007/s12262-013-0855-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2012] [Accepted: 01/16/2013] [Indexed: 12/17/2022] Open
Abstract
Prevention of secondary infection is currently the main goal of treatment for acute necrotizing pancreatitis. Colon was considered as the main origin of secondary infection. Our aim was to investigate whether prophylactic total colectomy would reduce the rate of bacterial translocation and infection of pancreatic necrosis. Forty-two Sprague-Dawley rats were used. Pancreatitis was created by ductal infusion of sodium taurocholate. Rats were divided into four groups: group-1, laparotomy + pancreatic ductal infusion of saline; group-2, laparotomy + pancreatic ductal infusion of sodium taurocholate; group-3, total colectomy + pancreatic ductal infusion of saline; and group-4, total colectomy + pancreatic ductal infusion of sodium taurocholate. Forty-eight hours later, tissue and blood samples were collected for microbiological and histopathological analysis. Total colectomy caused small bowel bacterial overgrowth with gram-negative and gram-positive microorganisms. Bacterial count of gram-negative rods in the small intestine and pancreatic tissue in rats with colectomy and acute pancreatitis were significantly higher than in rats with acute pancreatitis only (group-2 versus group-4; small bowel, p = <0.001; pancreas, p = 0.002). Significant correlation was found between proximal small bowel bacterial overgrowth and pancreatic infection (r = 0,836, p = 0.001). In acute pancreatitis, prophylactic total colectomy (which can mimic colonic cleansing and reduction of colonic flora) induces small bowel bacterial overgrowth, which is associated with increased bacterial translocation to the pancreas.
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Affiliation(s)
- Rahman Şenocak
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
| | - Taner Yigit
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
| | - Zafer Kılbaş
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
| | - Ali Kağan Coşkun
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
| | - Ali Harlak
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
| | - Mustafa Öner Menteş
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
| | - Abdullah Kılıç
- />Department of Microbiology, Gülhane Military Medical Academy, Etlik Ankara, Turkey
| | - Armağan Günal
- />Department of Pathology, Gülhane Military Medical Academy, Etlik Ankara, Turkey
| | - Orhan Kozak
- />Department of General Surgery, Gülhane Military Medical Academy, 06018 Ankara, Turkey
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Rosenfeld CS. Microbiome Disturbances and Autism Spectrum Disorders. Drug Metab Dispos 2015; 43:1557-71. [PMID: 25852213 DOI: 10.1124/dmd.115.063826] [Citation(s) in RCA: 146] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Accepted: 04/06/2015] [Indexed: 12/18/2022] Open
Abstract
Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined.
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Affiliation(s)
- Cheryl S Rosenfeld
- Bond Life Sciences Center, Thompson Center for Autism and Neurobehavioral Disorders, Genetics Area Program, and Department of Biomedical Sciences, University of Missouri, Columbia, Missouri
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Wang W, Chen SW, Zhu J, Zuo S, Ma YY, Chen ZY, Zhang JL, Chen GW, Liu YC, Wang PY. Intestinal alkaline phosphatase inhibits the translocation of bacteria of gut-origin in mice with peritonitis: mechanism of action. PLoS One 2015; 10:e0124835. [PMID: 25946026 PMCID: PMC4422672 DOI: 10.1371/journal.pone.0124835] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Accepted: 03/19/2015] [Indexed: 12/22/2022] Open
Abstract
Exogenous intestinal alkaline phosphatase (IAP), an enzyme produced endogenously at the brush edge of the intestinal mucosa, may mitigate the increase in aberrant intestinal permeability increased during sepsis. The aim of this study was to test the efficacy of the inhibitory effect of IAP on acute intestinal inflammation and to study the molecular mechanisms underlying IAP in ameliorating intestinal permeability. We used an in vivo imaging method to evaluate disease status and the curative effect of IAP. Two Escherichia coli (E.coli) B21 strains, carrying EGFP labeled enhanced green fluorescent protein (EGFP) and RFP labeled red fluorescent protein (RFP), were constructed as tracer bacteria and were administered orally to C57/B6N mice to generate an injection peritonitis (IP) model. The IP model was established by injecting inflammatory lavage fluid. C57/B6N mice bearing the tracer bacteria were subsequently treated with (IP+IAP group), or without IAP (IP group). IAP was administered to the mice via tail vein injections. The amount of tracer bacteria in the blood, liver, and lungs at 24 h post-injection was analyzed via flow cytometry (FCM), in vivo imaging, and Western blotting. Intestinal barrier function was measured using a flux assay with the macro-molecule fluorescein isothiocyanate dextran, molecular weight 40kD, (FD40). To elucidate the molecular mechanism underlying the effects of IAP, we examined the levels of ERK phosphorylation, and the expression levels of proteins in the ERK-SP1-VEGF and ERK-Cdx-2-Claudin-2 pathways. We observed that IAP inhibited the expression of Claudin-2, a type of cation channel-forming protein, and VEGF, a cytokine that may increase intestinal permeability by reducing the levels of dephosphorylated ERK. In conclusion, exogenous IAP shows a therapeutic effect in an injection peritonitis model. This including inhibition of bacterial translocation. Moreover, we have established an imaging methodology for live-animals can effectively evaluate intestinal permeability and aberrant bacterial translocation in IP models.
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Affiliation(s)
- Wei Wang
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Shan-Wen Chen
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Jing Zhu
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Shuai Zuo
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Yuan-Yuan Ma
- Experimental Animal Center, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Zi-Yi Chen
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Jun-Ling Zhang
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Guo-Wei Chen
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Yu-Cun Liu
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
| | - Peng-Yuan Wang
- Department of Surgery, Peking University First Hospital, Xi Shi Ku Street, Beijing, China
- * E-mail:
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Leal-Lopes C, Velloso FJ, Campopiano JC, Sogayar MC, Correa RG. Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies. J Diabetes Res 2015; 2015:284680. [PMID: 26347203 PMCID: PMC4544440 DOI: 10.1155/2015/284680] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 07/09/2015] [Indexed: 12/12/2022] Open
Abstract
The pancreas plays a central role in metabolism, allowing ingested food to be converted and used as fuel by the cells throughout the body. On the other hand, the pancreas may be affected by devastating diseases, such as pancreatitis, pancreatic adenocarcinoma (PAC), and diabetes mellitus (DM), which generally results in a wide metabolic imbalance. The causes for the development and progression of these diseases are still controversial; therefore it is essential to better understand the underlying mechanisms which compromise the pancreatic homeostasis. The interest in the study of the commensal microbiome increased extensively in recent years, when many discoveries have illustrated its central role in both human physiology and maintenance of homeostasis. Further understanding of the involvement of the microbiome during the development of pathological conditions is critical for the improvement of new diagnostic and therapeutic approaches. In the present review, we discuss recent findings on the behavior and functions played by the microbiota in major pancreatic diseases and provide further insights into its potential roles in the maintenance of pancreatic steady-state activities.
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Affiliation(s)
- Camila Leal-Lopes
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Fernando J. Velloso
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Julia C. Campopiano
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Mari C. Sogayar
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Ricardo G. Correa
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
- *Ricardo G. Correa:
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Oláh A, Romics Jr L. Enteral nutrition in acute pancreatitis: A review of the current evidence. World J Gastroenterol 2014; 20:16123-16131. [PMID: 25473164 PMCID: PMC4239498 DOI: 10.3748/wjg.v20.i43.16123] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 07/22/2014] [Indexed: 02/06/2023] Open
Abstract
The use of enteral feeding as part of the management of acute pancreatitis dates back almost two decades. This review describes the indications for and limitations of enteral feeding for the treatment of acute pancreatitis using up-to-date evidence-based data. A systematic review was carried out to analyse current data on the use of enteral nutrition in the management of acute pancreatitis. Relevant literature was analysed from the viewpoints of enteral vs parenteral feeding, early vs delayed enteral nutrition, nasogastric vs nasojejunal feeding, and early oral diet and immunonutrition, particularly glutamine and probiotic supplementation. Finally, current applicable guidelines and the effects of these guidelines on clinical practice are discussed. The latest meta-analyses suggest that enteral nutrition significantly reduces the mortality rate of severe acute pancreatitis compared to parenteral feeding. To maintain gut barrier function and prevent early bacterial translocation, enteral feeding should be commenced within the first 24 h of hospital admission. Also, the safety of nasogastric feeding, which eases the administration of enteral nutrients in the clinical setting, is likely equal to nasojejunal feeding. Furthermore, an early low-fat oral diet is potentially beneficial in patients with mild pancreatitis. Despite the initial encouraging results, the current evidence does not support the use of immunoenhanced nutrients or probiotics in patients with acute pancreatitis.
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van Baal MC, van Rens MJ, Geven CB, van de Pol FM, van den Brink IW, Hannink G, Nagtegaal ID, Peters WH, Rijkers GT, Gooszen HG. Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats. Pancreatology 2014; 14:470-7. [PMID: 25458667 DOI: 10.1016/j.pan.2014.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2014] [Revised: 09/30/2014] [Accepted: 10/02/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic prophylaxis and enteral nutrition contributed to the higher mortality rate. METHODS Male Sprague-Dawley rats were allocated to four groups: 1) acute pancreatitis (n = 9), 2) acute pancreatitis and probiotic prophylaxis (n = 10), 3) acute pancreatitis and enteral nutrition (n = 10), and 4) acute pancreatitis, probiotic prophylaxis and enteral nutrition (n = 11). Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Enteral nutrition, saline, probiotics and placebo were administered through a permanent jejunal feeding. Probiotics or placebo were administered starting 4 days before induction of pancreatitis and enteral nutrition 1 day before start until the end of the experiment, 6 days after induction of pancreatitis. Tissue samples and body fluids were collected for microbiological and histological examination. RESULTS In all animals, serum amylase was increased six hours after induction of pancreatitis. After fulfilling the experiment, no differences between groups were found in histological severity of pancreatitis, degree of discomfort, weight loss, histological examination of small bowel and bacterial translocation (all p > 0.05). Overall mortality was 10% without differences between groups (p = 0.54). CONCLUSION No negative association was found between prophylactic probiotics and enteral nutrition in acute pancreatitis. No new clues for a potential mechanism responsible for the higher mortality and bowel ischaemia in the PROPATRIA study were found.
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Affiliation(s)
- Mark C van Baal
- Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands.
| | - Michiel J van Rens
- Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands
| | - Christopher B Geven
- Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands
| | | | | | - Gerjon Hannink
- Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands
| | | | - Wilbert H Peters
- Dept. of Gastroenterology, Radboudumc, Nijmegen, The Netherlands
| | - Ger T Rijkers
- Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands
| | - Hein G Gooszen
- Dept. Operating Rooms/Evidence Based Surgery, Radboudumc, Nijmegen, The Netherlands.
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Effects of probiotic supplementation on markers of acute pancreatitis in rats. Curr Ther Res Clin Exp 2014; 70:136-48. [PMID: 24683225 DOI: 10.1016/j.curtheres.2009.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2008] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Intestinal barrier disruption followed by bacterial translocation seems to play a role in secondary pancreatic infection in acute pancreatitis. The use of probiotics as a possible adjuvant strategy in the treatment of acute pancreatitis needs to be investigated. OBJECTIVE The aim of this study was to determine the effects of dietary supplementation with a prophylactically administered multispecies probiotic mixture on the markers of acute pancreatitis and on the occurrence of bacterial translocation. METHODS Thirty adult male Wistar rats were randomly assigned to 1 of 3 groups of 10 rats each: (1) the PS group, in which the rats were given probiotic supplementation prior to induction of acute pancreatitis; (2) the WP group, in which the rats underwent surgery to induce acute pancreatitis without prior probiotic supplementation; and (3) the control group, in which the rats underwent sham surgery. For 14 days before surgery, animals in the PS group received a single daily dose containing ~1.2 × 10(9) colony-forming units of a probiotic mixture administered intragastrically as a bolus. On day 15, the animals underwent surgery to induce acute pancreatitis (PS and WP groups) or simulated surgery (control group). Blood samples were collected to determine leukocyte count, amylase and lipase activities, and glucose and calcium concentrations immediately before and 6 and 12 hours after the beginning of the procedure. Samples of pancreas, spleen, liver, and mesenteric lymph nodes were harvested for microbiologic and histopathologic analysis after the last blood sample collection. The pathologist examining the histopathology was blinded to treatment assignment. RESULTS The mean leukocyte count was significantly increased in the PS group compared with the WP group (P = 0.018), whereas the serum amylase and lipase activities and the serum glucose and calcium concentrations were not significantly different between the 2 groups. Comparing the risk for tissue colonization in the PS group with that of the WP group, the odds ratio (OR) for pancreas was 2.91 (95% CI, 0.13-67.10); liver, 66.55 (95% CI, 1.89-2282.66); spleen, 88.58 (95% CI, 3.04-2583.08); and mesenteric lymph nodes, 1.23 (95% CI, 0.06-25.48). When the risks for histopathologic changes were compared between the 2 groups, the OR for acinar necrosis was 1.73 (95% CI, 0.21-12.17); steatonecrosis, 12.08 (95% CI, 1.26-115.54); hemorrhage, 1.38 (95% CI, 0.21-9.53); and leukocyte infiltration, 5.91 (95% CI, 0.64-54.89). CONCLUSION Probiotic supplementation before the induction of acute pancreatitis was associated with a greater degree of bacterial translocation and pancreatic tissue damage in this animal model.
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Gou S, Yang Z, Liu T, Wu H, Wang C. Use of probiotics in the treatment of severe acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2014; 18:R57. [PMID: 24684832 PMCID: PMC4056604 DOI: 10.1186/cc13809] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 03/04/2014] [Indexed: 02/07/2023]
Abstract
Introduction Necrotic tissue infection can worsen the prognosis of severe acute pancreatitis (SAP), and probiotics have been shown to be beneficial in reducing the infection rate in animal experiments and primary clinical trials. However, the results of multicenter randomized clinical trials have been contradictory. Our aim in this study was to systematically review and quantitatively analyze all randomized controlled trials with regard to important outcomes in patients with predicted SAP who received probiotics. Methods A systematic literature search of the PubMed, Embase and Cochrane Library databases was conducted using specific search terms. Eligible studies were randomized controlled trials that compared the effects of probiotic with placebo treatment in patients with predicted SAP. Mean difference (MD), risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel fixed- and random-effects models. A meta-analysis on the use of probiotics in the treatment of critically ill patients was also performed to serve as a reference. Results In this study, 6 trials comprising an aggregate total of 536 patients were analyzed. Significant heterogeneities were observed in the type, dose, treatment duration and clinical effects of probiotics in these trials. Systematic analysis showed that probiotics did not significantly affect the pancreatic infection rate (RR = 1.19, 95% CI = 0.74 to 1.93; P = 0.47), total infections (RR = 1.09, 95% CI = 0.80 to 1.48; P = 0.57), operation rate (RR = 1.42, 95% CI = 0.43 to 3.47; P = 0.71), length of hospital stay (MD = 2.45, 95% CI = −2.71 to 7.60; P = 0.35) or mortality (RR = 0.72, 95% CI = 0.42 to 1.45; P = 0.25). Conclusions Probiotics showed neither beneficial nor adverse effects on the clinical outcomes of patients with predicted SAP. However, significant heterogeneity was noted between the trials reviewed with regard to the type, dose and treatment duration of probiotics, which may have contributed to the heterogeneity of the clinical outcomes. The current data are not sufficient to draw a conclusion regarding the effects of probiotics on patients with predicted SAP. Carefully designed clinical trials are needed to validate the effects of particular probiotics given at specific dosages and for specific treatment durations.
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Hypertonic saline solution reduces mesenteric microcirculatory dysfunctions and bacterial translocation in a rat model of strangulated small bowel obstruction. Shock 2014; 40:35-44. [PMID: 23644577 DOI: 10.1097/shk.0b013e318299d3fa] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
We examined the effects of hypertonic saline (HS) on inflammatory, metabolic variables, and bacterial translocation (BT) in rats submitted to intestinal obstruction and ischemia (IO). Male Wistar rats were submitted to IO and treated, 2 h thereafter, with lactated Ringer's (LR) (4 mL/kg per 5 min, i.v.) or HS (7.5% NaCl, 4 mL/kg per 5 min, i.v.). Twenty-four hours after IO, rats were also submitted to enterectomy/enteroanastomosis to resection of necrotized small bowel. Leukocyte-endothelial interactions were investigated by intravital microscopy and the expression of P-selectin and intercellular adhesion molecule 1 by immunohistochemistry. Bacterial cultures of mesenteric lymph nodes, liver, spleen, and blood were used to evaluate BT. Levels of chemokines (cytokine-induced neutrophil chemoattractants 1 and 2), insulin, and corticosterone were determined by enzyme-linked immunosorbent assay. Intestinal histology, serum urea and creatinine levels, and hepatic enzymes activities were performed to evaluate local and remote damage. Relative to IO and LR-treated rats, which exhibited increases in the number of rolling (1.5-fold), adhered (3.5-fold) and migrated (9.0-fold) leukocytes, and increased expression of P-selectin (3-fold) and intercellular adhesion molecule 1 (3-fold) on mesenteric microcirculation, treatment with HS followed by enterectomy reduced leukocyte-endothelial interactions and expression of both adhesion molecules to values attained in sham rats. Serum chemokines were normalized after treatment with both solutions followed by enterectomy. Hypertonic saline-treated rats demonstrated a significant reduction in BT to 50% in liver and spleen samples and bacteremia (14%), compared with 82% of BT in liver and spleen samples of IO and LR-treated rats and bacteremia (57%). Local intestinal damage was attenuated, and renal and hepatic function preserved by treatment with HS followed by enterectomy. Survival rate increased to 86% up to 15 days. Data presented suggest that HS solution followed by enterectomy reduces mesenteric microcirculatory dysfunctions and BT, attenuating local and remote damage in a model of strangulated small bowel obstruction.
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Urben LM, Wiedmar J, Boettcher E, Cavallazzi R, Martindale RG, McClave SA. Bugs or drugs: are probiotics safe for use in the critically ill? Curr Gastroenterol Rep 2014; 16:388. [PMID: 24986534 DOI: 10.1007/s11894-014-0388-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Probiotics are living microorganisms which have demonstrated many benefits in prevention, mitigation, and treatment of various disease states in critically ill populations. These diseases include antibiotic-associated diarrhea, Clostridium difficile diarrhea, ventilator-associated pneumonia, clearance of vancomycin-resistant enterococci from the GI tract, pancreatitis, liver transplant, major abdominal surgery, and trauma. However, their use has been severely limited due to a variety of factors including a general naïveté within the physician community, lack of regulation, and safety concerns. This article focuses on uses for probiotics in prevention and treatment, addresses current concerns regarding their use as well as proposing a protocol for safe use of probiotics in the critically ill patient.
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Affiliation(s)
- Lindsay M Urben
- Department of Pharmacy, University of Louisville Hospital, Louisville, KY, USA
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Burnett AF, Biju PG, Lui H, Hauer-Jensen M. Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model. Radiat Res 2013; 180:595-602. [PMID: 24219324 DOI: 10.1667/rr13330.1] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Countermeasures against radiation are critically needed. Ideally, these measures would be easy to store, easy to administer and have minimal toxicity. We used oral delivery of interleukin 11 (IL11) in mice exposed to lethal doses of total-body irradiation (TBI). Animals were given IL11 by gavage at various daily doses beginning 24 h after TBI, which continued for 5 days. At a TBI of 9.0 Gy, mice treated with IL11 had a 70% survival at 30 days compared with control group survival of 25% (P = 0.035). At 10.0 Gy, treated animals had 50% survival at 30 days compared with no survivors in the control group. Treated animals had significant improvement in intestinal mucosal surface area and crypt survival. In addition bacterial translocation of coliform bacteria was significantly less in the treated animals. Systemic absorption of IL11 was low in treated animals and effects on the hematopoietic cells were not seen. Serum citrulline levels rebounded significantly faster after irradiation in the IL11 treated animals, indicating quicker recovery of small intestine health. These data suggest that IL11 given orally protects the intestinal mucosa from radiation damage and that this compound is beneficial as a mitigating agent even when started 24 h after radiation exposure.
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Affiliation(s)
- Alexander F Burnett
- a Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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Persborn M, Gerritsen J, Wallon C, Carlsson A, Akkermans LMA, Söderholm JD. The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis. Aliment Pharmacol Ther 2013; 38:772-83. [PMID: 23957603 DOI: 10.1111/apt.12451] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2013] [Revised: 05/14/2013] [Accepted: 07/23/2013] [Indexed: 12/30/2022]
Abstract
BACKGROUND A total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. AIM To examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. METHODS Sixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and ⁵¹Cr-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. RESULTS Pouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P < 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P < 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. CONCLUSIONS Probiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.
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Affiliation(s)
- M Persborn
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton) 2013; 17:733-8. [PMID: 22817644 DOI: 10.1111/j.1440-1797.2012.01647.x] [Citation(s) in RCA: 156] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
AIM To investigate whether gut bacteria translocation occurs in end-stage renal disease patients and contributes to microinflammation in end-stage renal disease (ESRD). METHODS The subjects were divided into two groups: nondialysed ESRD patients (n = 30) and healthy controls (n = 10). Blood samples from all participants were subjected to bacterial 16S ribosomal DNA amplification and DNA pyrosequencing to determine the presence of bacteria, and the alteration of gut microbiomes were examined with the same methods. High-sensitive C-reactive protein and interleukin-6 were detected. Plasma D-lactate was tested for gut permeability. RESULTS Bacterial DNAs were detected in the blood of 20% (6/30) of the ESRD patients. All the observed genera in blood (Klebsiella spp, Proteus spp, Escherichia spp, Enterobacter spp, and Pseudomonas spp) were overgrown in the guts of the ESRD patients. Plasma D-lactate, High-sensitive C-reactive protein, and interleukin-6 levels were significantly higher in patients with bacterial DNA than those without. The control group showed the same results as that of patients without bacterial DNA. CONCLUSION Bacterial translocation occurs in ESRD patients and is associated with microinflammation in end stage renal disease.
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Affiliation(s)
- Feiqian Wang
- Dialysis Department of Nephrology Center, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Hooijmans CR, de Vries RBM, Rovers MM, Gooszen HG, Ritskes-Hoitinga M. The effects of probiotic supplementation on experimental acute pancreatitis: a systematic review and meta-analysis. PLoS One 2012; 7:e48811. [PMID: 23152810 PMCID: PMC3496732 DOI: 10.1371/journal.pone.0048811] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Accepted: 10/05/2012] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND In February 2008, the results of the PRObiotics in PAncreatitis TRIAl (PROPATRIA) were published. This study investigated the use of probiotics in patients suffering from severe acute pancreatitis. No differences between the groups were found for any of the primary endpoints. However, mortality in the probiotics group was significantly higher than in the placebo group. This result was unexpected in light of the results of the animal studies referred to in the trial protocol. We used the methods of systematic review and meta-analysis to take a closer look at the relation between the animal studies on probiotics and pancreatitis and the PROPATRIA-trial, focussing on indications for harmful effects and efficacy. METHODS AND RESULTS Both PubMed and Embase were searched for original articles concerning the effects of probiotics in experimental acute pancreatitis, yielding thirteen studies that met the inclusion criteria. Data on mortality, bacterial translocation and histological damage to the pancreas were extracted, as well as study quality indicators. Meta-analysis of the four animal studies published before PROPATRIA showed that probiotic supplementation did not diminish mortality, reduced the overall histopathological score of the pancreas and reduced bacterial translocation to pancreas and mesenteric lymph nodes. Comparable results were found when all relevant studies published so far were taken into account. CONCLUSIONS A more thorough analysis of all relevant animal studies carried out before (and after) the publication of the study protocol of the PROPATRIA trial could not have predicted the harmful effects of probiotics found in the PROPATRIA-trial. Moreover, meta-analysis of the preclinical animal studies did show evidence for efficacy. It may be suggested, however, that the most appropriate animal experiments in relation to the design of the human trial have not yet been conducted, which compromises a fair comparison between the results of the animal studies and the PROPATRIA trial.
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Affiliation(s)
- Carlijn R Hooijmans
- Radboud University Nijmegen Medical Centre, SYRCLE at Central Animal Laboratory, Nijmegen, The Netherlands.
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Gut bacterial translocation contributes to microinflammation in experimental uremia. Dig Dis Sci 2012; 57:2856-62. [PMID: 22615020 DOI: 10.1007/s10620-012-2242-0] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Accepted: 05/03/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Microinflammation frequently develops in chronic uremia with pathological intestinal changes. However, the relationship between gut bacterial translocation and microinflammation in uremia has not been widely investigated. AIM This study aimed to investigate whether gut microbiome dysbiosis and translocation occurred in experimental uremia, and whether they consequently contributed to microinflammation. METHODS Forty rats underwent surgical renal mass 5/6 ablation. The surviving (uremic group, n = 21) and healthy (sham group, n = 20) rats were used in the experiment. Postoperative blood, livers, spleens, and mesenteric lymph nodes (MLNs) were subjected to bacterial 16S ribosomal DNA amplification to determine if bacteria were present. Bacterial genomic DNA samples from the MLNs and colon were amplified with specific primers designed by the 16S rRNA sequence of the species obtained from blood, livers, and spleens. Pyrosequencing was used to analyze the colonic microbiome of each subject. Intestinal permeability to (99m)Tc-DTPA, plasma hs-CRP, and IL-6 were measured. RESULTS Bacterial DNA in extraintestinal sites and altered colonic microbiomes were detected in some rats in the uremic group. Bacterial genomic DNA in MLNs and colon were obtained by primers specific for bacterial species observed from blood, livers, and spleens of identical individuals. Intestinal permeability, plasma hs-CRP, and IL-6 levels were statistically higher in the uremic group compared with the sham group. Plasma hs-CRP and IL-6 were significantly higher in uremic rats with bacterial DNA in their blood than in those without. CONCLUSIONS Gut microbiome dysbiosis occurs and bacteria translocate to the systemic and lymph circulation, thereby contributing to microinflammation in experimental uremia.
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