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Ishikawa D, Watanabe H, Nomura K, Zhang X, Maruyama T, Odakura R, Koma M, Shibuya T, Osada T, Fukuda S, Nakahara T, Terauchi J, Nagahara A, Yamada T. Patient-donor similarity and donor-derived species contribute to the outcome of fecal microbiota transplantation for ulcerative colitis. J Crohns Colitis 2025; 19:jjaf054. [PMID: 40168084 DOI: 10.1093/ecco-jcc/jjaf054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Indexed: 04/03/2025]
Abstract
BACKGROUND AND AIMS Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching. METHODS Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy. RESULTS Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P = .027), immunosuppressants (P = .049), and biologics (P = .029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P = .03, LTR; P = .05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P < .05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P < .05). CONCLUSIONS This study provides important insights for developing patient-tailored FMT-based therapies for UC.
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Affiliation(s)
- Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Metagen Therapeutics, Inc., Yamagata, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Hikaru Watanabe
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Metagen Therapeutics, Inc., Yamagata, Japan
| | - Kei Nomura
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Xiaochen Zhang
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Takafumi Maruyama
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Rina Odakura
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Masao Koma
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Taro Osada
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Shinji Fukuda
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Metagen Therapeutics, Inc., Yamagata, Japan
- Institute for Advanced Biosciences, Keio University, Yamagata, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kanagawa, Japan
- Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan
| | | | | | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
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Chen W, Xu L, Wang L, Shan YN, Li Y, Zhu JS. Qing-Re-Hua-Shi Decoction ameliorates DSS-induced colitis by modulating multiple signaling pathways and remodeling the gut microbiota and metabolite profile. Front Cell Infect Microbiol 2025; 15:1541289. [PMID: 40242025 PMCID: PMC11999956 DOI: 10.3389/fcimb.2025.1541289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 03/13/2025] [Indexed: 04/18/2025] Open
Abstract
Background Clinically, Qing-Re-Hua-Shi Decoction (QRHSD) has been clinically used to treat ulcerative colitis (UC) with satisfactory outcomes and minimal side effects. However, its molecular mechanisms remain unclear. Purpose This study investigates the effects of QRHSD on DSS-induced colitis in mice, employing multi-omics analyses, including RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology analysis. Methods The chemical composition of QRHSD was analyzed using quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A UC mice model was induced by 3% DSS for 7 days. The effects and mechanisms of QRHSD on UC were evaluated via hematoxylin and eosin, immunofluorescence assay, flow cytometry, western blot, RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology. Correlation analyses and validation experiments explored links between transcriptomic, microbiome, metabolomic profiles, and UC-related clinical indices. Results UPLC-Q-TOF/MS identified 55 compounds in QRHSD. QRHSD significantly reduced clinical activity, histological changes, and inflammatory factors in UC mice, regulated Th17/Treg balance, and enhanced intestinal barrier integrity. 16S rRNA analysis showed that QRHSD altered gut microbiota composition, increasing beneficial bacteria (e.g., Lactobacillus) and decreasing harmful bacteria (e.g., Morganella). Non-targeted metabolomics revealed 507 metabolites associated with UC amelioration, enriched in pathways like bile secretion, ABC transporters, and amino acid biosynthesis. RNA-seq analysis, network pharmacology, and experimental verification showed that QRHSD significantly regulated key signaling pathways, including PI3K/AKT, NF-κB, and MAPK signaling pathways. Finally, correlation analysis highlighted connections among UC-related clinical factors, gut microbiota, and metabolites. Conclusion QRHSD could modulate the gut microbiota, metabolic homeostasis, and multiple signal pathways in the treatment of DSS-induced UC, revealing the mechanism of traditional Chinese medicine therapy for UC.
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Affiliation(s)
- Wei Chen
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lin Xu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Long Wang
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-nan Shan
- School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Yan Li
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jin-shui Zhu
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Murgiano M, Bartocci B, Puca P, di Vincenzo F, Del Gaudio A, Papa A, Cammarota G, Gasbarrini A, Scaldaferri F, Lopetuso LR. Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools. Int J Mol Sci 2025; 26:3059. [PMID: 40243712 PMCID: PMC11988433 DOI: 10.3390/ijms26073059] [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: 01/12/2025] [Revised: 03/18/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.
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Affiliation(s)
- Marco Murgiano
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Bianca Bartocci
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Pierluigi Puca
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Federica di Vincenzo
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Angelo Del Gaudio
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Alfredo Papa
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Cammarota
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Franco Scaldaferri
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Loris Riccardo Lopetuso
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Università degli Studi Link, 00165 Rome, Italy
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Hodgkiss R, Acharjee A. Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167618. [PMID: 39662756 DOI: 10.1016/j.bbadis.2024.167618] [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: 09/20/2024] [Revised: 11/20/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.
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Affiliation(s)
- Rebecca Hodgkiss
- College of Medicine and Health, Cancer and Genomic Sciences, University of Birmingham, B15 2TT Birmingham, UK
| | - Animesh Acharjee
- College of Medicine and Health, Cancer and Genomic Sciences, University of Birmingham, B15 2TT Birmingham, UK; Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, B15 2TT Birmingham, UK; MRC Health Data Research UK (HDR), Midlands Site, UK; Centre for Health Data Research, University of Birmingham, B15 2TT, UK.
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Liu Z, Wang M, Hu Y, Li J, Gong W, Guo X, Song S, Zhu B. Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:422-432. [PMID: 39212113 DOI: 10.1002/jsfa.13839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/26/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated. RESULTS The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT. CONCLUSION Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Zhengqi Liu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
- National Engineering Research Center of Seafood, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian, PR China
| | - Menghui Wang
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Yuanyuan Hu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Jinjin Li
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Wei Gong
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Xiaoming Guo
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Shuang Song
- National Engineering Research Center of Seafood, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian, PR China
| | - Beiwei Zhu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
- National Engineering Research Center of Seafood, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian, PR China
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Yin Y, Yang T, Tian Z, Shi C, Yan C, Li H, Du Y, Li G. Progress in the investigation of the Firmicutes/Bacteroidetes ratio as a potential pathogenic factor in ulcerative colitis. J Med Microbiol 2025; 74. [PMID: 39886918 DOI: 10.1099/jmm.0.001966] [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] [Indexed: 02/01/2025] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that presents significant challenges in terms of treatment owing to a pronounced likelihood of recurrence and an elevated risk of cancer development, thereby imposing substantial risks on affected individuals. The gut microbiota of Firmicutes and Bacteroidetes (F/B) can affect diseases associated with IBD, which is also a risk factor for breast cancer. This review discusses the hazards associated with UC, highlights the existing disparities in UC-associated gut microbiome research, explores the concept of the F/B ratio and scrutinizes its correlation with UC. Moreover, the differences in the F/B ratios between healthy individuals and those with UC were thoroughly examined. These findings suggest that an elevated F/B ratio may promote the occurrence and progression of UC. Consequently, the F/B ratio may play a significant role in UC by influencing gut microbiota composition and inflammatory responses, suggesting that future research should focus on this ratio as a potential biomarker for disease progression and therapeutic targets in managing UC.
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Affiliation(s)
- Yu Yin
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Tiezheng Yang
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Ziyue Tian
- Hainan Provincial People's Hospital, Haikou 570100, PR China
| | - Chong Shi
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Chengqiu Yan
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Hui Li
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Yu Du
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Guofeng Li
- Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen 518000, PR China
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Hu Y, Wu Z, Yang X, Ding J, Wang Q, Fang H, Zhu L, Hu M. Reduced gut microbiota diversity in ulcerative colitis patients with latent tuberculosis infection during vedolizumab therapy: insights on prophylactic anti-tuberculosis effects. BMC Microbiol 2024; 24:543. [PMID: 39731099 DOI: 10.1186/s12866-024-03705-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 12/13/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND The gut microbiota plays a pivotal role in ulcerative colitis (UC) development. This study explores the impact of latent tuberculosis infection (LTBI) on the gut microbiota in UC and assesses changes during vedolizumab treatment, investigating prophylactic anti-tuberculosis therapy. RESULTS This cohort study included adult patients with UC receiving vedolizumab treatment at Jinhua Hospital, Zhejiang University from April 2021 to December 2022. Patients were divided into LTBI (n = 24) and non-LTBI (n = 21) groups. Patients in the LTBI group were further subdivided into prophylactic (n = 13) and non-prophylactic (n = 11) groups. Clinical and fecal samples were collected pre- and post-vedolizumab treatment for the LTBI groups and pre-treatment for the non-LTBI group. The gut microbiota was analyzed using 16 S rRNA sequencing. Patients in the non-LTBI group exhibited higher diversity indices. Vedolizumab demonstrated efficacy in the LTBI group, with clinical response and remission rates of 83.3% and 75.0%, respectively. The gut microbiota diversity in the LTBI group increased post-vedolizumab treatment, and receiving prophylactic isoniazid showed no significant difference in vedolizumab treatment response compared to not receiving prophylactic isoniazid. Microbiota changes were similar between groups, with an increase in [Ruminococcus] expression after vedolizumab treatment. CONCLUSIONS This cohort study, conducted at a single center, highlights that LTBI can reduce gut microbiota diversity among adult patient with UC. The observed efficacy of vedolizumab treatment in the LTBI group indicates a potential association with microbiota changes. However, mono-isoniazid exhibited limited impact, underscoring the potential of vedolizumab as a promising candidate for prophylactic anti-tuberculosis treatment in the context of UC.
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Affiliation(s)
- Yibing Hu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China
| | - Zhenping Wu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China
| | - Xiaoyun Yang
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China
| | - Jin Ding
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China
| | - Qunying Wang
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China
| | - Hao Fang
- Department of Traumatology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, P. R. China
| | - Lujian Zhu
- Department of Infection, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, P. R. China
| | - Minli Hu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China.
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Biagioli M, Di Giorgio C, Massa C, Marchianò S, Bellini R, Bordoni M, Urbani G, Roselli R, Lachi G, Morretta E, Piaz FD, Charlier B, Fiorillo B, Catalanotti B, Cari L, Nocentini G, Ricci P, Distrutti E, Festa C, Sepe V, Zampella A, Monti MC, Fiorucci S. Microbial-derived bile acid reverses inflammation in IBD via GPBAR1 agonism and RORγt inverse agonism. Biomed Pharmacother 2024; 181:117731. [PMID: 39657506 DOI: 10.1016/j.biopha.2024.117731] [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: 09/20/2024] [Revised: 11/22/2024] [Accepted: 12/03/2024] [Indexed: 12/12/2024] Open
Abstract
The interplay between the dysbiotic microbiota and bile acids is a critical determinant for development of a dysregulated immune system in inflammatory bowel disease (IBD). Here we have investigated the fecal bile acid metabolome, gut microbiota composition, and immune responses in IBD patients and murine models of colitis and found that IBD associates with an elevated excretion of primary bile acids while secondary, allo- and oxo- bile acids were reduced. These changes correlated with the disease severity, mucosal expression of pro-inflammatory cytokines and chemokines, and reduced inflow of anti-inflammatory macrophages and Treg in the gut. Analysis of bile acids metabolome in the feces allowed the identification of five bile acids: 3-oxo-DCA, 3-oxo-LCA, allo-LCA, iso-allo-LCA and 3-oxo-UDCA, whose excretion was selectively decreased in IBD patients and diseased mice. By transactivation assay and docking calculations all five bile acids were shown to act as GPBAR1 agonists and RORγt inverse agonists, skewing Th17/Treg ratio and macrophage polarization toward an M2 phenotype. In a murine model of colitis, administration of 3-oxo-DCA suffices to reverse colitis development and intestinal dysbiosis in a GPBAR1-dependent manner. In vivo administration of 3-oxo-DCA to colitic mice also reverses disease severity and RORγt activation induced by a RORγt agonist and IL-23, a Th17 inducing cytokine. These results demonstrated that intestinal excretion of 3-oxoDCA, a dual GPBAR1 agonist and RORγt inverse agonist, is reduced in IBD and in models of colitis and its restitution protects against colitis development, highlighting a potential role for this agent in IBD management.
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Affiliation(s)
- Michele Biagioli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | | | - Carmen Massa
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Silvia Marchianò
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Rachele Bellini
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Martina Bordoni
- Bar Pharmaceuticals s.r.l., Via Gramsci 88/A, Reggio Emilia 42124, Italy
| | - Ginevra Urbani
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Rosalinda Roselli
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Ginevra Lachi
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Elva Morretta
- Department of Pharmacy, University of Salerno, Salerno, Italy
| | - Fabrizio Dal Piaz
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy
| | - Bruno Charlier
- University hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy
| | - Bianca Fiorillo
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Bruno Catalanotti
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Luigi Cari
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Giuseppe Nocentini
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Patrizia Ricci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | | | - Carmen Festa
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Valentina Sepe
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Angela Zampella
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Stefano Fiorucci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
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9
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Li DH, Li ZW, Sun Q, Wang L, Ning SB. Lower fecal microbiota transplantation ameliorates ulcerative colitis by eliminating oral-derived Fusobacterium nucleatum and virulence factor. Gut Pathog 2024; 16:42. [PMID: 39118149 PMCID: PMC11311926 DOI: 10.1186/s13099-024-00633-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 07/17/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Recently, the oral oncobacterium Fusobacterium nucleatum (F. nucleatum), has been linked with ulcerative colitis (UC). Here, we aim to investigate whether Fecal Microbiota Transplantation (FMT) can alleviate UC by restoring gut microbiota and eliminating oral-derived F. nucleatum and virulence factor fadA. METHOD C57BL/6J mice were randomly divided into a healthy control group (HC), Dextran Sulfate Sodium group (DSS), oral inoculation group (OR), upper FMT group (UFMT), and lower FMT group (LFMT). Disease activity index, body weight, survival rate, and histopathological scores were used to measure the severity of colitis. The function of the intestinal mucosal barrier was evaluated by performing immunohistochemical staining of the tight junction protein Occludin. Real-time PCR was used to assess the relative abundance of the nusG gene and the virulence gene fadA. Cytokine levels were detected by ELISA. Full-length sequencing of 16S rRNA was used to analyze the changes and composition of gut microbiota. FINDINGS Oral incubation of F. nucleatum further exacerbated the severity of colitis and gut dysbiosis. Peptostreptococcaceae, Enterococcaceae, and Escherichia coli were significantly enriched in OR mice. However, LFMT mice showed an obvious decrease in disease activity and were more effective in restoring gut microbiota and eliminating F. nucleatum than UFMT mice. Bacteroidota, Lachnospiraceae, and Prevotellaceae were mainly enriched bacteria in LFMT mice. In addition, Genera such as Lactobacillus, Allobaculum, and Bacteroidales were found negative correlation with TNF-α, IL-1β, and IL-6. Genera like Romboutsia, Escherichia Shigella, Enterococcus, and Clostridium were found positively correlated with TNF-α, IL-1β, and IL-6. CONCLUSIONS Oral incubation of F. nucleatum further exacerbates the severity and dysbiosis in DSS-induced colitis mice. Besides, lower tract FMT can ameliorate colitis by restoring the gut microbiota diversity and eliminating F. nucleatum and virulence factor fadA.
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Affiliation(s)
- Dong-Hao Li
- Department of Gastroenterology, Air Force Medical Center of Chinese People's Liberation Army, Beijing, China
| | - Zong-Wei Li
- Department of Gastroenterology, Air Force Medical Center of Chinese People's Liberation Army, Beijing, China
| | - Qi Sun
- Department of Gastroenterology, Air Force Medical Center of Chinese People's Liberation Army, Beijing, China
| | - Lei Wang
- Department of Gastroenterology, Air Force Medical Center of Chinese People's Liberation Army, Beijing, China
| | - Shou-Bin Ning
- Department of Gastroenterology, Air Force Medical Center of Chinese People's Liberation Army, Beijing, China.
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10
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Sohn MB, Monaco C, Gill SR. An optimal normalization method for high sparse compositional microbiome data. PLoS Comput Biol 2024; 20:e1012338. [PMID: 39102403 PMCID: PMC11326560 DOI: 10.1371/journal.pcbi.1012338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 08/15/2024] [Accepted: 07/17/2024] [Indexed: 08/07/2024] Open
Abstract
In many omics data, including microbiome sequencing data, we are only able to measure relative information. Various computational or statistical methods have been proposed to extract absolute (or biologically relevant) information from this relative information; however, these methods are under rather strong assumptions that may not be suitable for multigroup (more than two groups) and/or longitudinal outcome data. In this article, we first introduce the minimal assumption required to extract absolute from relative information. This assumption is less stringent than those imposed in existing methods, thus being applicable to multigroup and/or longitudinal outcome data. We then propose the first normalization method that works under this minimal assumption. The optimality and validity of the proposed method and its beneficial effects on downstream analysis are demonstrated in extensive simulation studies, where existing methods fail to produce consistent performance under the minimal assumption. We also demonstrate its application to real microbiome datasets to determine biologically relevant microbes to a specific disease/condition.
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Affiliation(s)
- Michael B Sohn
- Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, United States of America
| | - Cynthia Monaco
- Medicine, University of Rochester Medical Center, Rochester, New York, United States of America
- Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America
| | - Steven R Gill
- Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America
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11
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Zhang JT, Zhang N, Dong XT, Wang XR, Ma HW, Liu YD, Li MR. Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis: A post-consensus systematic review and meta-analysis. World J Clin Cases 2024; 12:4691-4702. [PMID: 39070844 PMCID: PMC11235499 DOI: 10.12998/wjcc.v12.i21.4691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/28/2024] [Accepted: 06/19/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary. AIM To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis. METHODS The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively. RESULTS We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups. CONCLUSION FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.
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Affiliation(s)
- Jin-Tao Zhang
- Department of Clinical Medicine, School of Medicine, Nankai University, Tianjin 300071, China
| | - Nan Zhang
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Xue-Tao Dong
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Xiao-Ran Wang
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Hong-Wen Ma
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Yan-Di Liu
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Mu-Ran Li
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
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12
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Williams LM, Cao S. Harnessing and delivering microbial metabolites as therapeutics via advanced pharmaceutical approaches. Pharmacol Ther 2024; 256:108605. [PMID: 38367866 PMCID: PMC10985132 DOI: 10.1016/j.pharmthera.2024.108605] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/05/2024] [Accepted: 02/08/2024] [Indexed: 02/19/2024]
Abstract
Microbial metabolites have emerged as key players in the interplay between diet, the gut microbiome, and host health. Two major classes, short-chain fatty acids (SCFAs) and tryptophan (Trp) metabolites, are recognized to regulate inflammatory, immune, and metabolic responses within the host. Given that many human diseases are associated with dysbiosis of the gut microbiome and consequent reductions in microbial metabolite production, the administration of these metabolites represents a direct, multi-targeted treatment. While a multitude of preclinical studies showcase the therapeutic potential of both SCFAs and Trp metabolites, they often rely on high doses and frequent dosing regimens to achieve systemic effects, thereby constraining their clinical applicability. To address these limitations, a variety of pharmaceutical formulations approaches that enable targeted, delayed, and/or sustained microbial metabolite delivery have been developed. These approaches, including enteric encapsulations, esterification to dietary fiber, prodrugs, and nanoformulations, pave the way for the next generation of microbial metabolite-based therapeutics. In this review, we first provide an overview of the roles of microbial metabolites in maintaining host homeostasis and outline how compromised metabolite production contributes to the pathogenesis of inflammatory, metabolic, autoimmune, allergic, infectious, and cancerous diseases. Additionally, we explore the therapeutic potential of metabolites in these disease contexts. Then, we provide a comprehensive and up-to-date review of the pharmaceutical strategies that have been employed to enhance the therapeutic efficacy of microbial metabolites, with a focus on SCFAs and Trp metabolites.
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Affiliation(s)
- Lindsey M Williams
- Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, United States
| | - Shijie Cao
- Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, United States.
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13
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Dai J, Jiang M, Wang X, Lang T, Wan L, Wang J. Human-derived bacterial strains mitigate colitis via modulating gut microbiota and repairing intestinal barrier function in mice. BMC Microbiol 2024; 24:96. [PMID: 38521930 PMCID: PMC10960398 DOI: 10.1186/s12866-024-03216-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 02/07/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. RESULTS In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus, which were positively correlated with gut barrier function, while suppressing Odoribacter, Rikenella, Oscillibacter and Parasutterella, which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects. CONCLUSIONS Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.
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Affiliation(s)
- Juanjuan Dai
- Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China
| | - Mingjie Jiang
- Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China
| | - Xiaoxin Wang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Lang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Leilei Wan
- Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jingjing Wang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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14
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Zhang L, Agrawal M, Ng SC, Jess T. Early-life exposures and the microbiome: implications for IBD prevention. Gut 2024; 73:541-549. [PMID: 38123972 PMCID: PMC11150004 DOI: 10.1136/gutjnl-2023-330002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 11/29/2023] [Indexed: 12/23/2023]
Abstract
The early-life period is one of microbiome establishment and immune maturation. Early-life exposures are increasingly being recognised to play an important role in IBD risk. The composition of functions of the gut microbiome in the prenatal, perinatal, and postnatal period may be crucial towards development of health or disease, including IBD, later in life. We herein present a comprehensive summary of the interplay between early-life factors and microbiome perturbations, and their association with risk of IBD. In addition, we provide an overview of host and external factors in early life that are known to impact gut microbiome maturation and exposures implicated in IBD risk. Considering the emerging concept of IBD prevention, we propose strategies to minimise maternal and offspring exposure to potentially harmful variables and recommend protective measures during pregnancy and the postpartum period. This holistic view of early-life factors and microbiome signatures among mothers and their offspring will help frame our current understanding of their importance towards IBD pathogenesis and frame the roadmap for preventive strategies.
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Affiliation(s)
- Lin Zhang
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Manasi Agrawal
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, New York, USA
| | - Siew C Ng
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
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15
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Amara J, Itani T, Hajal J, Bakhos JJ, Saliba Y, Aboushanab SA, Kovaleva EG, Fares N, Mondragon AC, Miranda JM. Circadian Rhythm Perturbation Aggravates Gut Microbiota Dysbiosis in Dextran Sulfate Sodium-Induced Colitis in Mice. Nutrients 2024; 16:247. [PMID: 38257139 PMCID: PMC10819604 DOI: 10.3390/nu16020247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/09/2024] [Accepted: 01/10/2024] [Indexed: 01/24/2024] Open
Abstract
Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM), sixty male C57BL/6J mice were initially divided to two groups, with the shifted group (n = 30) exposed to circadian shifts for three months and the non-shifted group (n = 30) kept under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 h light-dark cycle, followed by another five days under a reversed light-dark cycle. At the end of the three months, a colitis was induced by 2% DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n = 15 per group): sham group non-shifted (Sham-NS), sham group shifted (Sham-S), DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition via DNA extraction, followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, the GM composition was modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings show possible interplay between circadian rhythm disruption, GM dynamics and colitis pathogenesis.
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Affiliation(s)
- Joseph Amara
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut 1104 2020, Lebanon; (J.A.); (J.H.); (Y.S.)
| | - Tarek Itani
- Laboratoire de Microbiologie, Faculté de Pharmacie, Université Saint Joseph, Beirut 1104 2020, Lebanon;
| | - Joelle Hajal
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut 1104 2020, Lebanon; (J.A.); (J.H.); (Y.S.)
| | - Jules-Joel Bakhos
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut 1104 2020, Lebanon; (J.A.); (J.H.); (Y.S.)
| | - Youakim Saliba
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut 1104 2020, Lebanon; (J.A.); (J.H.); (Y.S.)
| | - Saied A. Aboushanab
- Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, Yekaterinburg 620002, Russia; (S.A.A.); (E.G.K.)
| | - Elena G. Kovaleva
- Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, Yekaterinburg 620002, Russia; (S.A.A.); (E.G.K.)
| | - Nassim Fares
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut 1104 2020, Lebanon; (J.A.); (J.H.); (Y.S.)
| | - Alicia C. Mondragon
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain;
| | - Jose Manuel Miranda
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain;
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16
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Blesl A, Wurm P, Waschina S, Gröchenig HP, Novacek G, Primas C, Reinisch W, Kutschera M, Illiasch C, Hennlich B, Steiner P, Koch R, Tillinger W, Haas T, Reicht G, Mayer A, Ludwiczek O, Miehsler W, Steidl K, Binder L, Reider S, Watschinger C, Fürst S, Kump P, Moschen A, Aden K, Gorkiewicz G, Högenauer C. Prediction of Response to Systemic Corticosteroids in Active UC by Microbial Composition-A Prospective Multicenter Study. Inflamm Bowel Dis 2024; 30:9-19. [PMID: 37463118 PMCID: PMC10769779 DOI: 10.1093/ibd/izad126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. METHODS In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. RESULTS Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. CONCLUSION Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.
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Affiliation(s)
- Andreas Blesl
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Philipp Wurm
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Silvio Waschina
- Christian-Albrechts-University Kiel, Institute for Human Nutrition and Food Science, Nutriinformatics, Kiel, Germany
| | | | - Gottfried Novacek
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Christian Primas
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Walter Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Maximilian Kutschera
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | | | | | | | - Robert Koch
- Medical University of Innsbruck, Innsbruck, Austria
| | | | | | | | | | | | | | - Karin Steidl
- Brothers of Saint John of God Hospital, St. Veit an der Glan, Austria
| | - Lukas Binder
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Simon Reider
- Department of Internal Medicine 2 (Gastroenterology and Hepatology), Faculty of Medicine, Kepler University Hospital, Johannes Kepler University, Linz, Austria
- Christian Doppler Laboratory for Mucosal Immunology, Johannes Kepler University Linz, Linz, Austria
| | - Christina Watschinger
- Department of Internal Medicine 2 (Gastroenterology and Hepatology), Faculty of Medicine, Kepler University Hospital, Johannes Kepler University, Linz, Austria
- Christian Doppler Laboratory for Mucosal Immunology, Johannes Kepler University Linz, Linz, Austria
| | - Stefan Fürst
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Patrizia Kump
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Alexander Moschen
- Department of Internal Medicine 2 (Gastroenterology and Hepatology), Faculty of Medicine, Kepler University Hospital, Johannes Kepler University, Linz, Austria
- Christian Doppler Laboratory for Mucosal Immunology, Johannes Kepler University Linz, Linz, Austria
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany
- Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany
| | | | - Christoph Högenauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
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17
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Pandey H, Jain D, Tang DWT, Wong SH, Lal D. Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease. Intest Res 2024; 22:15-43. [PMID: 37935653 PMCID: PMC10850697 DOI: 10.5217/ir.2023.00080] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 11/09/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
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Affiliation(s)
| | | | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi, India
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Florio M, Crudele L, Moschetta A, Gadaleta RM. Discovering the Nutrition-Microbiota Interplay in Inflammatory Bowel Disease: Are We There Yet? Endocrinology 2024:333-371. [DOI: 10.1007/978-3-031-35064-1_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Do KH, Ko SH, Kim KB, Seo K, Lee WK. Comparative Study of Intestinal Microbiome in Patients with Ulcerative Colitis and Healthy Controls in Korea. Microorganisms 2023; 11:2750. [PMID: 38004761 PMCID: PMC10673479 DOI: 10.3390/microorganisms11112750] [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: 09/30/2023] [Revised: 11/07/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
Ulcerative colitis (UC) poses a contemporary medical challenge, with its exact cause still eluding researchers. This is due to various factors, such as the rising incidence, diagnostic complexities, and difficulties associated with its management. We compared the intestinal microbiome of patients with UC to that of healthy controls to determine the qualitative and quantitative changes associated with UC that occur in the intestinal microbiota. The intestinal bacterial abundance in 40 Korean patients with UC and 25 healthy controls was assayed using via next-generation sequencing. There were five major phyla in both groups: Firmicutes (UC patients: 51.12%; healthy controls: 46.90%), Bacteroidota (UC patients: 37.04%; healthy controls: 40.34%), Proteobacteria (UC patients: 6.01%; healthy controls: 11.05%), Actinobacteriota (UC patients: 5.71%; healthy controls: 1.56%), and Desulfobacteriota (UC patients: 0.13%; healthy controls: 0.14%). Firmicutes was more prevalent in patients with UC (51.12%) compared to that of healthy controls (46.90%). Otherwise, Bacteroidota was more prevalent in healthy controls (40.34%) compared to patients with UC (37.04%). Although there was no significant difference, our results showed a substantially lower gut microbiome diversity in patients with UC (mean: 16.5; 95% confidence interval (CI) = 14.956-18.044) than in healthy controls (mean: 17.84; 95% CI = 15.989-19.691), the beta diversity and the flora structure of the microbiome in patients with UC differed from those in healthy controls. This will be helpful for the development of new treatment options and lay the groundwork for future research on UC. To understand the disease mechanism, it is essential to define the different types of microbes in the guts of patients with UC.
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Affiliation(s)
- Kyung-Hyo Do
- College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea;
| | - Seung-Hyun Ko
- GutBiomeTech Co., Ltd., Cheongju 28644, Republic of Korea
| | - Ki Bae Kim
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Republic of Korea
| | - Kwangwon Seo
- College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea;
| | - Wan-Kyu Lee
- College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea;
- GutBiomeTech Co., Ltd., Cheongju 28644, Republic of Korea
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20
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Di Ciaula A, Bonfrate L, Khalil M, Portincasa P. The interaction of bile acids and gut inflammation influences the pathogenesis of inflammatory bowel disease. Intern Emerg Med 2023; 18:2181-2197. [PMID: 37515676 PMCID: PMC10635993 DOI: 10.1007/s11739-023-03343-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 06/08/2023] [Indexed: 07/31/2023]
Abstract
Bile acids (BA) are amphipathic molecules originating from cholesterol in the liver and from microbiota-driven biotransformation in the colon. In the gut, BA play a key role in fat digestion and absorption and act as potent signaling molecules on the nuclear farnesoid X receptor (FXR) and membrane-associated G protein-coupled BA receptor-1 (GPBAR-1). BA are, therefore, involved in the maintenance of gut barrier integrity, gene expression, metabolic homeostasis, and microbiota profile and function. Disturbed BA homeostasis can activate pro-inflammatory pathways in the gut, while inflammatory bowel diseases (IBD) can induce gut dysbiosis and qualitative and/or quantitative changes of the BA pool. These factors contribute to impaired repair capacity of the mucosal barrier, due to chronic inflammation. A better understanding of BA-dependent mechanisms paves the way to innovative therapeutic tools by administering hydrophilic BA and FXR agonists and manipulating gut microbiota with probiotics and prebiotics. We discuss the translational value of pathophysiological and therapeutic evidence linking BA homeostasis to gut inflammation in IBD.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy.
| | - Mohamad Khalil
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
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21
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Liu Y, Duan H, Chen Y, Zhang C, Zhao J, Narbad A, Tian F, Zhai Q, Yu L, Chen W. Intraspecific difference of Latilactobacillus sakei in inflammatory bowel diseases: Insights into potential mechanisms through comparative genomics and metabolomics analyses. IMETA 2023; 2:e136. [PMID: 38868211 PMCID: PMC10989848 DOI: 10.1002/imt2.136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 08/22/2023] [Accepted: 08/30/2023] [Indexed: 06/14/2024]
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of the gastrointestinal tract that have become a global health burden. Studies have revealed that Latilactobacillus sakei can effectively alleviate various immune diseases, including colitis, rheumatoid arthritis, and metabolic disorders. Here, we obtained 72 strains of L. sakei from 120 fermentation and fecal samples across China. In total, 16 strains from different sources were initially screened in an in vitro Caco-2 model induced by dextran sulfate sodium. Subsequently, six strains (four exhibiting effectiveness and two exhibiting ineffectiveness) were selected for further validation in an in vivo colitis mouse model. The results demonstrated that L. sakei strains exhibited varying degrees of amelioration of the colitis disease process. Notably, L. sakei CCFM1267, the most effective strain, significantly restored colon length and tight-junction protein expression, and reduced the levels of cytokines and associated inflammatory enzymes. Moreover, L. sakei CCFM1267 upregulated the abundance of Enterorhabdus, Alloprevotella, and Roseburia, leading to increased levels of acetic acid and propionic acid. Conversely, the other four strains (L. sakei QJSSZ1L4, QJSSZ4L10, QGZZYRHMT1L6, and QGZZYRHMT2L6) only exhibited a partial remission effect, while L. sakei QJSNT1L10 displayed minimal impact. Therefore, L. sakei CCFM1267 and QJSNT1L10 were selected for further exploration of the mechanisms underlying their differential mitigating effects. Comparative genomics analysis revealed significant variations between the two strains, particularly in genes associated with carbohydrate-active enzymes, such as the glycoside hydrolase family, which potentially contribute to the diverse profiles of short-chain fatty acids in vivo. Additionally, metabolome analysis demonstrated that acetylcholine and indole-3-acetic acid were the main differentiating metabolites of the two strains. Therefore, the strains of L. sakei exhibited varying degrees of effectiveness in alleviating IBD-related symptoms, and the possible reasons for these variations were attributed to discrepancies in the carbohydrate-active enzymes and metabolites among the strains.
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Affiliation(s)
- Yaru Liu
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
| | - Hui Duan
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
| | - Ying Chen
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
| | - Chengcheng Zhang
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
| | - Jianxin Zhao
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
- National Engineering Research Center for Functional FoodJiangnan UniversityWuxiChina
- International Joint Research Laboratory for ProbioticsJiangnan UniversityWuxiChina
| | - Arjan Narbad
- International Joint Research Laboratory for ProbioticsJiangnan UniversityWuxiChina
- Gut Health and Microbiome Institute Strategic ProgrammeQuadram Institute BioscienceNorwichUK
| | - Fengwei Tian
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
- International Joint Research Laboratory for ProbioticsJiangnan UniversityWuxiChina
| | - Qixiao Zhai
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
- International Joint Research Laboratory for ProbioticsJiangnan UniversityWuxiChina
| | - Leilei Yu
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
- International Joint Research Laboratory for ProbioticsJiangnan UniversityWuxiChina
| | - Wei Chen
- State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxiChina
- School of Food Science and TechnologyJiangnan UniversityWuxiChina
- National Engineering Research Center for Functional FoodJiangnan UniversityWuxiChina
- International Joint Research Laboratory for ProbioticsJiangnan UniversityWuxiChina
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22
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Hsia K, Zhao N, Chung M, Algarrahi K, Montaser Kouhsari L, Fu M, Chen H, Singh S, Michaud DS, Jangi S. Alterations in the Fungal Microbiome in Ulcerative Colitis. Inflamm Bowel Dis 2023; 29:1613-1621. [PMID: 37221272 PMCID: PMC10547232 DOI: 10.1093/ibd/izad082] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Indexed: 05/25/2023]
Abstract
BACKGROUND Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic activity and treatment exposure in ulcerative colitis. METHODS We analyzed data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry. We evaluated the fungal composition of fecal samples from 98 patients with ulcerative colitis across endoscopic activity (n = 43), endohistologic activity (n = 41), and biologic exposure (n = 82). Across all subgroups, we assessed fungal diversity and differential abundance of taxonomic groups. RESULTS We identified 500 unique fungal amplicon sequence variants across the cohort of 82 patients, dominated by phylum Ascomycota. Compared with endoscopic remission, patients with endoscopic activity had increased Saccharomyces (log2 fold change = 4.54; adjusted P < 5 × 10-5) and increased Candida (log2 fold change = 2.56; adjusted P < .03). After adjusting for age, sex, and biologic exposure among patients with endoscopic activity, Saccharomyces (log2 fold change = 7.76; adjusted P < 1 × 10-15) and Candida (log2 fold change = 7.28; adjusted P< 1 × 10-8) remained enriched during endoscopic activity compared with quiescence. CONCLUSIONS Endoscopic inflammation in ulcerative colitis is associated with an expansion of Saccharomyces and Candida compared with remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.
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Affiliation(s)
- Katie Hsia
- Department of Medicine, Tufts Medical Center, Boston, MA, USA
| | - Naisi Zhao
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA
| | - Mei Chung
- Friedman School of Nutrition and Science Policy, Tufts University, Boston, MA, USA
| | - Khalid Algarrahi
- Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA
| | | | - May Fu
- Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA
| | - Hannah Chen
- Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Dominique S Michaud
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA
| | - Sushrut Jangi
- Division of Gastroenterology, Department of Medicine, Tufts Medical Center, Boston, MA, USA
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23
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Liu J, Fang H, Hong N, Lv C, Zhu Q, Feng Y, Wang B, Tian J, Yu Y. Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis. Microbiol Spectr 2023; 11:e0145723. [PMID: 37199618 PMCID: PMC10269848 DOI: 10.1128/spectrum.01457-23] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 05/09/2023] [Indexed: 05/19/2023] Open
Abstract
Patients with ulcerative colitis (UC) have low response rates to anti-integrin medications, necessitating the identification of noninvasive biomarkers for predicting remission to anti-integrin therapy. In this study, patients with moderate to severe UC commencing anti-integrin therapy (n = 29), inactive to mild UC patients (n = 13), and healthy controls (n = 11) were selected. Besides clinical evaluation, fecal samples were collected at baseline and week 14 from moderate to severe UC patients. The clinical remission was defined based on the Mayo score. Fecal samples were assessed with 16S rRNA gene sequencing, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry (GC-MS). We identified that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. GC-MS analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared to the nonremission group at baseline. Finally, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961). We identified significantly higher phylum level diversity of Verrucomicrobiota in remission than the nonremission groups at baseline. Notably, the combination of gut microbiome and metabonomic profiles improved the diagnosis of early remission to anti-integrin therapy. IMPORTANCE It is reported that patients with ulcerative colitis (UC) have low response rates to anti-integrin medications in the latest VARSITY study. Therefore, our primary goals were to discover differences in the gut microbiome and metabonomics patterns between early remission and nonremission patients and to explore the diagnostic value in predicting clinical remission to anti-integrin therapy accurately. In this study, we found that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. Gas chromatography-mass spectrometry analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared with the nonremission group at baseline. Notably, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961).
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Affiliation(s)
- Jie Liu
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Huaying Fang
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
- Endoscopy Center Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Na Hong
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
- Endoscopy Center Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Chaolan Lv
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
- Endoscopy Center Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Qihua Zhu
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Yinping Feng
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Bo Wang
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Jiashuang Tian
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Yue Yu
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
- Endoscopy Center Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
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24
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Haas AL, Zemke AC, Melvin JA, Armbruster CR, Hendricks MR, Moore J, Nouraie SM, Thibodeau PH, Lee SE, Bomberger JM. Iron bioavailability regulates Pseudomonas aeruginosa interspecies interactions through type VI secretion expression. Cell Rep 2023; 42:112270. [PMID: 36930643 PMCID: PMC10586262 DOI: 10.1016/j.celrep.2023.112270] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 12/16/2022] [Accepted: 03/01/2023] [Indexed: 03/18/2023] Open
Abstract
The cystic fibrosis (CF) respiratory tract harbors pathogenic bacteria that cause life-threatening chronic infections. Of these, Pseudomonas aeruginosa becomes increasingly dominant with age and is associated with worsening lung function and declining microbial diversity. We aimed to understand why P. aeruginosa dominates over other pathogens to cause worsening disease. Here, we show that P. aeruginosa responds to dynamic changes in iron concentration, often associated with viral infection and pulmonary exacerbations, to become more competitive via expression of the TseT toxic effector. However, this behavior can be therapeutically targeted using the iron chelator deferiprone to block TseT expression and competition. Overall, we find that iron concentration and TseT expression significantly correlate with microbial diversity in the respiratory tract of people with CF. These findings improve our understanding of how P. aeruginosa becomes increasingly dominant with age in people with CF and provide a therapeutically targetable pathway to help prevent this shift.
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Affiliation(s)
- Allison L Haas
- Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Anna C Zemke
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
| | - Jeffrey A Melvin
- Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Catherine R Armbruster
- Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Matthew R Hendricks
- Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - John Moore
- Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
| | - Seyed Mehdi Nouraie
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
| | - Patrick H Thibodeau
- Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Stella E Lee
- Division of Otolaryngology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
| | - Jennifer M Bomberger
- Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
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25
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Patel A, Krishna SG, Patel K, Gray DM, Mumtaz K, Stanich PP, Hinton A, Hussan H. Rising Rates of Severe Obesity in Adults Younger Than 50 Correspond to Rise in Hospitalizations for Non-malignant Gastrointestinal Disease. Dig Dis Sci 2023; 68:554-563. [PMID: 35704253 DOI: 10.1007/s10620-022-07589-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 06/03/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Colorectal cancer incidence is rising in adults < 50 years old, possibly due to obesity. Non-malignant colorectal conditions are understudied in this population. We hypothesize that developing severe obesity in young adulthood also corresponds with increased hospitalization rates for non-malignant colorectal conditions. METHODS We examined annual percent change (APC) in the prevalence of obesity in adults < 50 using the 2009-2014 National Health and Nutrition Examination Survey. Using the 2010-2014 Nationwide Readmission Database, we then compared yearly hospitalization trends for various gastrointestinal conditions and their outcomes in adults < 50 with severe obesity vs. no obesity. RESULTS The prevalence of obesity increased in adults < 50 years in 2009-2014. This increase was most pronounced for severe obesity (APC of + 12.8%). The rate of patients with severe obesity < 50 who were admitted for gastrointestinal diseases has increased by 7.76% per year in 2010-2014 (p < 0.001). This increase was > 10% per year for colorectal conditions such Clostridium difficile infections (APC + 17.3%, p = 0.002), inflammatory bowel disease (APC + 13.1%, p = 0.001), and diverticulitis (APC + 12.7%, p = 0.002). The hospitalization rate for chronic liver diseases and acute pancreatitis also increased by 12.2% and 10.0% per year, respectively (p < 0.01). In contrast, young adults without obesity had lower hospitalization rate for most gastrointestinal diseases. Furthermore, adults with no obesity had lower mortality rates for appendicitis, diverticulitis, pancreatitis and chronic liver diseases than adults with severe obesity. CONCLUSION Our data suggest that increased adiposity in young adults is associated with more hospitalization and worse outcomes for infectious/inflammatory gastrointestinal conditions. Future prevention strategies are warranted to ameliorate these trends.
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Affiliation(s)
- Arsheya Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA.
| | - Somashekar G Krishna
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Kishan Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA
| | - Darrell M Gray
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA
| | - Khalid Mumtaz
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA
| | - Peter P Stanich
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA
| | - Alice Hinton
- Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH, USA
| | - Hisham Hussan
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Ohio State University, 395 W 12th Ave, Suite 240, Columbus, OH, 43210, USA
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
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26
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Reznikov EA, Suskind DL. Current Nutritional Therapies in Inflammatory Bowel Disease: Improving Clinical Remission Rates and Sustainability of Long-Term Dietary Therapies. Nutrients 2023; 15:nu15030668. [PMID: 36771373 PMCID: PMC9920576 DOI: 10.3390/nu15030668] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/19/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) includes a spectrum of chronic immune-mediated intestinal diseases thought to be related to the complex interaction between the host immune system and the intestinal microbiome. Research supports the use of nutritional therapy in IBD; however, it is not routinely used in clinical practice. This literature review seeks to advance the understanding of diet and its effect in IBD with a focus on both Crohn's Disease (CD) and Ulcerative Colitis (UC). The contribution of diet to the development and treatment of IBD cannot be overstated. In both pediatric as well as adult IBD, nutritional interventions have been shown to improve clinical symptoms as well as inflammatory burden. The impact of dietary intervention is best exemplified through the use of Exclusive Enteral Nutrition (EEN) in CD. EEN and clinical research on exclusionary whole food diets-Crohn's Disease Exclusion Diet (CDED), Specific Carbohydrate Diet (SCD), low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, and Mediterranean Diet-are discussed within this review. Current clinical literature supports the elimination of detrimental components and the incorporation of low processed whole foods in the diet. Additional prospective and longitudinal dietary studies on sustainable and long-term dietary options, along with a deeper understanding of the mechanism, are needed to further advance the role of nutritional interventions in IBD.
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27
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Zhang W, Pang A, Tan B, Xin Y, Liu Y, Xie R, Zhang H, Yang Q, Deng J, Chi S. Tryptophan metabolism and gut flora profile in different soybean protein induced enteritis of pearl gentian groupers. Front Nutr 2022; 9:1014502. [PMID: 36601073 PMCID: PMC9807032 DOI: 10.3389/fnut.2022.1014502] [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: 08/08/2022] [Accepted: 11/18/2022] [Indexed: 12/23/2022] Open
Abstract
The substitution of high-level soy meals for fish meal (FM) generally leads to fish enteritis, accompanied by significant variations in gut flora. Relevant studies have pointed out a close relationship between tryptophan metabolism mediated by gut flora and vertebrate inflammatory bowel disease. Present study examines the role of tryptophan metabolism and gut flora profile in fish enteritis caused by different soybean meals. The 960 groupers were randomly assigned into 4 groups (n = 4), which including: (1) FM (the control group, fed with 50% FM feed), (2) SBM40 (replacing 40% FM with soybean meal), (3) SPC40 (replacing 40% FM with soybean protein concentrate), and (4) FSBM40 (replacing 40% FM with fermented soybean meal). Under average temperature and natural light, the groupers were cultivated with feeds of iso-nitrogen and iso-lipid for 10 weeks. The results showed that soybean meal feeds at all experimental levels had negative effects on fish gut physiology and growth performance. Typical enteritis features and fluctuations of immune system occur, which can be observed in the enzyme activities of total superoxide dismutase and lysozyme and in the contents of immunoglobulin M, complement 3 and complement 4. 16SrDNA high-throughput sequencing indicated that it greatly influenced the gut flora with the abundance of maleficent bacteria, like Vibrio, amplified with increasing dietary soybean meals. According to the "3 + 2" full-length transcriptome sequencing, soy meals at the three experimental levels inhibited the key gene expressions of tryptophan metabolic pathway in fish gut, however, there are some differences in the types of key genes that are inhibited. The canonical correlation analysis showed that the changes in key gene expressions in tryptophan metabolic pathway had a positive correlation with the expressions of pro-inflammatory genes (P < 0.05) and negatively correlated with the expression of anti-inflammatory genes (P < 0.05). It is speculated from this study that tryptophan metabolism is closely related to fish soy meal-related enteritis, and the abnormal tryptophan metabolism caused by intestinal flora imbalance may play an important role. In the future research, we can further study the tolerance of fish to soy meals feed from two aspects of tryptophan metabolism and intestinal flora changes.
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Affiliation(s)
- Wei Zhang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Aobo Pang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Beiping Tan
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China,*Correspondence: Beiping Tan,
| | - Yu Xin
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Yu Liu
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Ruitao Xie
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Haitao Zhang
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Qihui Yang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Junming Deng
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
| | - Shuyan Chi
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, Guangdong, China,Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, Guangdong, China,Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, Guangdong, China
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Monma T, Iwamoto J, Ueda H, Tamamushi M, Kakizaki F, Konishi N, Yara S, Miyazaki T, Hirayama T, Ikegami T, Honda A. Evaluation of gut dysbiosis using serum and fecal bile acid profiles. World J Clin Cases 2022; 10:12484-12493. [PMID: 36579096 PMCID: PMC9791502 DOI: 10.12998/wjcc.v10.i34.12484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/25/2022] [Accepted: 11/04/2022] [Indexed: 12/02/2022] Open
Abstract
Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites, and toxic substances can disrupt the barrier function of the intestinal wall, leading to the development of various diseases. Decreased levels of Clostridium subcluster XIVa (XIVa) are associated with the intestinal dysbiosis found in inflammatory bowel disease (IBD) and Clostridium difficile infection (CDI). Since XIVa is a bacterial group responsible for the conversion of primary bile acids (BAs) to secondary BAs, the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid (DCA)/[DCA + cholic acid (CA)] in feces orserum. For example, serum DCA/(DCA+CA) was significantly lower in IBD patients than in healthy controls, even in the remission period. These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation. Another report showed that a reduced serum DCA/(DCA + CA) ratio could predict susceptibility to CDI. Thus, the BA profile, particularly the ratio of secondary to primary BAs, can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.
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Affiliation(s)
- Tadakuni Monma
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Junichi Iwamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Hajime Ueda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Makoto Tamamushi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Fumio Kakizaki
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Naoki Konishi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Shoichiro Yara
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Teruo Miyazaki
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Takeshi Hirayama
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Tadashi Ikegami
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Akira Honda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
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29
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Hu Y, Chen Z, Xu C, Kan S, Chen D. Disturbances of the Gut Microbiota and Microbiota-Derived Metabolites in Inflammatory Bowel Disease. Nutrients 2022; 14:5140. [PMID: 36501169 PMCID: PMC9735443 DOI: 10.3390/nu14235140] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/10/2022] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized as a chronic and recurrent inflammatory disease whose pathogenesis is still elusive. The gut microbiota exerts important and diverse effects on host physiology through maintaining immune balance and generating health-benefiting metabolites. Many studies have demonstrated that IBD is associated with disturbances in the composition and function of the gut microbiota. Both the abundance and diversity of gut microbiota are dramatically decreased in IBD patients. Furthermore, some particular classes of microbiota-derived metabolites, principally short-chain fatty acids, tryptophan, and its metabolites, and bile acids have also been implicated in the pathogenesis of IBD. In this review, we aim to define the disturbance of gut microbiota and the key classes of microbiota-derived metabolites in IBD pathogenesis. In addition, we also focus on scientific evidence on probiotics, not only on the molecular mechanisms underlying the beneficial effects of probiotics on IBD but also the challenges it faces in safe and appropriate application.
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Affiliation(s)
- Yongjia Hu
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Zhouzhou Chen
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Chengchen Xu
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Shidong Kan
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Daijie Chen
- School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China
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Wan C, Qian WW, Liu W, Pi X, Tang MT, Wang XL, Gu Q, Li P, Zhou T. Exopolysaccharide from Lactobacillus rhamnosus ZFM231 alleviates DSS-induced colitis in mice by regulating gut microbiota. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2022; 102:7087-7097. [PMID: 35707876 DOI: 10.1002/jsfa.12070] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 06/01/2022] [Accepted: 06/16/2022] [Indexed: 05/26/2023]
Abstract
BACKGROUND The exopolysaccharides (EPS) produced by Lactobacillus and other probiotics are associated with many benefits, such as immune regulation, antioxidant properties, antitumor effect, and regulation of intestinal microbe homeostasis. In the present study, the modulatory effect of EPS produced by Lactobacillus rhamnosus ZFM231 on the intestinal flora of mice with inflammatory bowel disease induced by dextran sulfate solution was investigated. RESULTS Results indicated that weight loss, colonic length, the disease activity index score and colonic tissue damage in mice were significantly improved by EPS treatment. Compared with the model group, in the EPS-treated group, the diversity of and the composition of gut microbiota at both phylum and genus levels were found to recover to the levels of normal group, indicating the effective modulation on gut microbiota by EPS; short-chain fatty acids, including acetic acid, propionic acid and butyric acid produced by intestinal microbial metabolism, increased significantly; the level of anti-inflammatory factor transforning growth factor-β significantly increased and the level of pro-inflammatory factor tumor necrosis factor-α significantly decreased in the colonic cells of EPS-treated mice. CONCLUSION It is clear that EPS produced by L. rhamnosus ZFM231 could find application in functional foods with the property of anti-ulcerative colitis. The experimental results provide new insights into the probiotic effect of EPS. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Cheng Wan
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Wen-Wen Qian
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Wei Liu
- Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China
| | - Xionge Pi
- Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China
| | - Meng-Ting Tang
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Xiao-Lin Wang
- Faulty of Food Science, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, China
| | - Qing Gu
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Ping Li
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Tao Zhou
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
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31
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Dietary Efficacy Evaluation by Applying a Prediction Model Using Clinical Fecal Microbiome Data of Colorectal Disease to a Controlled Animal Model from an Obesity Perspective. Microorganisms 2022; 10:microorganisms10091833. [PMID: 36144434 PMCID: PMC9505706 DOI: 10.3390/microorganisms10091833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/06/2022] [Accepted: 09/11/2022] [Indexed: 11/17/2022] Open
Abstract
Obesity associated with a Western diet such as a high-fat diet (HFD) is a known risk factor for inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this study, we aimed to develop fecal microbiome data-based deep learning algorithms for the risk assessment of colorectal diseases. The effects of a HFD and a candidate food (Nypa fruticans, NF) on IBD and CRC risk reduction were also evaluated. Fecal microbiome data were obtained from 109 IBD patients, 111 CRC patients, and 395 healthy control (HC) subjects by 16S rDNA amplicon sequencing. IBD and CRC risk assessment prediction models were then constructed by deep learning algorithms. Dietary effects were evaluated based on fecal microbiome data from rats fed on a regular chow diet (RCD), HFD, and HFD plus ethanol extracts or water extracts of NF. There were significant differences in taxa when IBD and CRC were compared with HC. The diagnostic performance (area under curve, AUC) of the deep learning algorithm was 0.84 for IBD and 0.80 for CRC prediction. Based on the rat fecal microbiome data, IBD and CRC risks were increased in HFD-fed rats versus RCD-fed rats. Interestingly, in the HFD-induced obesity model, the IBD and CRC risk scores were significantly lowered by the administration of ethanol extracts of NF, but not by the administration of water extracts of NF. In conclusion, changes in the fecal microbiome of obesity by Western diet could be important risk factors for the development of IBD and CRC. The risk prediction model developed in this study could be used to evaluate dietary efficacy.
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Sinha A, Li Y, Mirzaei MK, Shamash M, Samadfam R, King IL, Maurice CF. Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis. MICROBIOME 2022; 10:105. [PMID: 35799219 PMCID: PMC9264660 DOI: 10.1186/s40168-022-01275-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/13/2022] [Indexed: 05/03/2023]
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown. RESULTS Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs. CONCLUSIONS Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease. Video Abstract.
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Affiliation(s)
- Anshul Sinha
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
| | - Yue Li
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China
| | - Mohammadali Khan Mirzaei
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
- Institute of Virology, Helmholtz Center Munich and Technical University of Munich, 85764, Neuherberg, Bavaria, Germany
| | - Michael Shamash
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
| | - Rana Samadfam
- Charles River Laboratories, 22022 Transcanadienne, Senneville, QC, H9X 3R3, Canada
| | - Irah L King
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.
- McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, Canada.
| | - Corinne F Maurice
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.
- McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, Canada.
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Wang Z, Chen Y, Wang W, Huang C, Hu Y, Johnston L, Wang F. Dietary Supplementation With Fine-Grinding Wheat Bran Improves Lipid Metabolism and Inflammatory Response via Modulating the Gut Microbiota Structure in Pregnant Sow. Front Microbiol 2022; 13:835950. [PMID: 35418966 PMCID: PMC8999112 DOI: 10.3389/fmicb.2022.835950] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
This study investigated the effects of fine-grinding wheat bran on pregnant sow body condition, lipid metabolism, inflammatory response, and gut microbiota. In this study, wheat bran was crushed into three particle sizes. A total of 60 Landrace × Yorkshire second parity sows were allotted to two groups: CWB (a diet containing coarse wheat bran with particle size of 605 μm) and FWB (a diet containing fine wheat bran with particle size of 438 μm). Fine-grinding wheat bran had higher soluble dietary fiber concentration, swelling capacity, water-holding capacity, and fermentability than coarse wheat bran. Pregnant sows fed FWB throughout pregnancy had lower body weight and fat deposition than sows fed CWB. And the piglet body weight at birth of the FWB group was remarkably increased. Serum concentrations of lipids (triglycerides, total cholesterol, and free fatty acid), interleukin 6, leptin, and resistin were decreased on day 90 of pregnancy by fine wheat bran supplementation. Feeding FWB significantly decreased abundance of Firmicutes and dramatically increased the abundance of Bacteroidetes at phylum level. At genus level, the abundance of Terrisporobacter was decreased in FWB feeding sows, but the abundance of Parabacteroides was increased. Fecal total short-chain fatty acids, propionate, and butyrate contents were markedly increased in the FWB group. The results suggested that the physicochemical properties of finely ground wheat bran had been improved. Dietary supplementation with fine wheat bran changed the gut microbiota structure and enhanced the short-chain fatty acids level, which improved the maternal body condition, metabolic and inflammatory status, and reproductive performance in sows.
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Affiliation(s)
- Zijie Wang
- State Key Lab of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing, China
| | - Yifan Chen
- College of Animal Science and Technology, Hebei Agricultural University, Baoding, China
| | - Wenhui Wang
- State Key Lab of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing, China
| | - Caiyun Huang
- College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Yongfei Hu
- State Key Lab of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing, China
| | - Lee Johnston
- Swine Nutrition and Production, West Central Research and Outreach Center, University of Minnesota, Morris, MN, United States
| | - Fenglai Wang
- State Key Lab of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing, China
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Cortes GM, Marcialis MA, Bardanzellu F, Corrias A, Fanos V, Mussap M. Inflammatory Bowel Disease and COVID-19: How Microbiomics and Metabolomics Depict Two Sides of the Same Coin. Front Microbiol 2022; 13:856165. [PMID: 35391730 PMCID: PMC8981987 DOI: 10.3389/fmicb.2022.856165] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 02/21/2022] [Indexed: 12/11/2022] Open
Abstract
The integrity of the gastrointestinal tract structure and function is seriously compromised by two pathological conditions sharing, at least in part, several pathogenetic mechanisms: inflammatory bowel diseases (IBD) and coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IBD and COVID-19 are marked by gut inflammation, intestinal barrier breakdown, resulting in mucosal hyperpermeability, gut bacterial overgrowth, and dysbiosis together with perturbations in microbial and human metabolic pathways originating changes in the blood and fecal metabolome. This review compared the most relevant metabolic and microbial alterations reported from the literature in patients with IBD with those in patients with COVID-19. In both diseases, gut dysbiosis is marked by the prevalence of pro-inflammatory bacterial species and the shortfall of anti-inflammatory species; most studies reported the decrease in Firmicutes, with a specific decrease in obligately anaerobic producers short-chain fatty acids (SCFAs), such as Faecalibacterium prausnitzii. In addition, Escherichia coli overgrowth has been observed in IBD and COVID-19, while Akkermansia muciniphila is depleted in IBD and overexpressed in COVID-19. In patients with COVID-19, gut dysbiosis continues after the clearance of the viral RNA from the upper respiratory tract and the resolution of clinical symptoms. Finally, we presented and discussed the impact of gut dysbiosis, inflammation, oxidative stress, and increased energy demand on metabolic pathways involving key metabolites, such as tryptophan, phenylalanine, histidine, glutamine, succinate, citrate, and lipids.
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Affiliation(s)
- Gian Mario Cortes
- Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Monserrato, Italy
| | - Maria Antonietta Marcialis
- Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Monserrato, Italy
| | - Flaminia Bardanzellu
- Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Monserrato, Italy
| | - Angelica Corrias
- Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Monserrato, Italy
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Monserrato, Italy
| | - Michele Mussap
- Laboratory Medicine, Department of Surgical Sciences, School of Medicine, University of Cagliari, Monserrato, Italy
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Xu P, Lv T, Dong S, Cui Z, Luo X, Jia B, Jeon CO, Zhang J. Association between intestinal microbiome and inflammatory bowel disease: insights from bibliometric analysis. Comput Struct Biotechnol J 2022; 20:1716-1725. [PMID: 35495114 PMCID: PMC9019919 DOI: 10.1016/j.csbj.2022.04.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 04/05/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
Intestinal microbiota has been increasingly studied in the field of IBD over the last 20 years. The gut microbiome, metabolites, and their corresponding host signaling pathways are highly associated with IBD. Probiotics may relieve IBD as a complementary therapy. The pathogenesis and treatment strategies of IBD need to be further studied. The gut microbiome is highly linked to inflammatory bowel disease (IBD). A total of 3890 publications related to the two terms from 2000 to 2020 were extracted from the Web of Science Core Collection to study the association from a bibliometric perspective. Publications on this topic have grown rapidly since 2008. The United States and Harvard University are the country and institution with the largest number of publications, respectively. Inflammatory Bowel Diseases is the most productive journal with 211 published articles. The most influential journal in this field is Gut with 13,359 citations. The co-citation analysis of references showed that the IBD-related topics with the highest focus are “gut microbiota,” “metagenomics,” “bacterial community,” “fecal microbiota transplantation,” “probiotics,” and “colitis-associated colorectal cancer.” Keyword cluster and keyword burst analyses showed that “gut microbiota,” “metagenomics,” and “fecal microbiota transplantation” are currently the most researched topics in the field of IBD. The literature in this field is mainly distributed between alterations of the intestinal microbiota, microbial metabolites, and related host signaling pathways. Probiotic treatment also frequently appears in literature. This bibliometric analysis can guide future research and promote the development of the field of gut microbiome and IBD.
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Piestansky J, Olesova D, Matuskova M, Cizmarova I, Chalova P, Galba J, Majerova P, Mikus P, Kovac A. Amino acids in inflammatory bowel diseases: Modern diagnostic tools and methodologies. Adv Clin Chem 2022; 107:139-213. [PMID: 35337602 DOI: 10.1016/bs.acc.2021.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Amino acids are crucial building blocks of living organisms. Together with their derivatives, they participate in many intracellular processes to act as hormones, neuromodulators, and neurotransmitters. For several decades amino acids have been studied for their potential as markers of various diseases, including inflammatory bowel diseases. Subsequent improvements in sample pretreatment, separation, and detection methods have enabled the specific and very sensitive determination of these molecules in multicomponent matrices-biological fluids and tissues. The information obtained from targeted amino acid analysis (biomarker-based analytical strategy) can be further used for early diagnostics, to monitor the course of the disease or compliance of the patients. This review will provide an insight into current knowledge about inflammatory bowel diseases, the role of proteinogenic amino acids in intestinal inflammation and modern analytical techniques used in its diagnosis and disease activity monitoring. Current advances in the analysis of amino acids focused on sample pretreatment, separation strategy, or detection methods are highlighted, and their potential in clinical laboratories is discussed. In addition, the latest clinical data obtained from the metabolomic profiling of patients suffering from inflammatory bowel diseases are summarized with a focus on proteinogenic amino acids.
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Affiliation(s)
- Juraj Piestansky
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia; Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Dominika Olesova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Michaela Matuskova
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Ivana Cizmarova
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Petra Chalova
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Jaroslav Galba
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Petra Majerova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Peter Mikus
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia; Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Andrej Kovac
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
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Ishikawa D, Zhang X, Nomura K, Seki N, Haraikawa M, Haga K, Shibuya T, Kim YG, Nagahara A. A Randomized Placebo-Controlled Trial of Combination Therapy With Post-triple-antibiotic-therapy Fecal Microbiota Transplantation and Alginate for Ulcerative Colitis: Protocol. Front Med (Lausanne) 2022; 9:779205. [PMID: 35273972 PMCID: PMC8902497 DOI: 10.3389/fmed.2022.779205] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
Background Fecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate. Methods and Analysis This trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint. Discussion The FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC. Clinical Trial Registration https://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.
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Affiliation(s)
- Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.,Department of Intestinal Microbiota Therapy, Juntendo University School of Medicine, Tokyo, Japan
| | - Xiaochen Zhang
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kei Nomura
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Natsumi Seki
- Research Center for Drug Discovery, Faculty of Pharmacy, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
| | - Mayuko Haraikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Keiichi Haga
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yun-Gi Kim
- Research Center for Drug Discovery, Faculty of Pharmacy, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.,Department of Intestinal Microbiota Therapy, Juntendo University School of Medicine, Tokyo, Japan
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Li C, Wang M, Chen X, Chen W. Taraxasterol ameliorates dextran sodium sulfate-induced murine colitis via improving intestinal barrier and modulating gut microbiota dysbiosis. Acta Biochim Biophys Sin (Shanghai) 2022; 54:340-349. [PMID: 35538040 PMCID: PMC9827818 DOI: 10.3724/abbs.2022019] [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] [Indexed: 11/25/2022] Open
Abstract
Taraxasterol (TAX) has been proven to prevent and treat inflammatory diseases. However, the effects of TAX on intestinal barrier and the diversity, structure, and function of gut microbiota have yet to be elucidated in dextran sodium sulfate (DSS)-induced colitis mice. Our objectives are to evaluate the effect of TAX on intestinal barrier and its impact on gut microbiota. Herein, immunofluorescence analysis is conducted to determine the expressions of tight junction (ZO-1) and mucin (Mucin-2) proteins. The abundance, diversity, and function of fecal colonies are investigated by using 16S rDNA sequencing, and the influence of TAX on the gut microbiota in mice is also analyzed. Our results suggest that TAX attenuates the symptoms in DSS-induced colitis mice by reducing the DAI score, increasing colon length, alleviating histopathological damage of colon tissues, and improving intestinal barrier. 16S rDNA sequencing of fecal samples indicates that TAX intervention has a regulatory effect on DSS-induced gut microbiota dysbiosis at different taxonomic levels. TAX increases microbial diversity that is reduced by DSS. It normalizes the relative abundance of and the ratio of /. In addition, treatment with TAX has a better effect on the function of metabolisms, such as nucleotide, lipid, and bile acid metabolism. These findings suggest that TAX may be a good candidate for the remission of colitis, which is related to improving intestinal barrier and modulating gut microbiota.
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Affiliation(s)
- Chen Li
- Department of General SurgeryAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China
| | - Meng Wang
- Department of General SurgeryAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China
| | - Xiqi Chen
- Department of General SurgeryAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China
| | - Wei Chen
- Department of GastroenterologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai201203China,Correspondence address. Tel: +86-18217789965; E-mail:
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Gerasimidis K, Nichols B, McGowan M, Svolos V, Papadopoulou R, Kokkorou M, Rebull M, Bello Gonzalez T, Hansen R, Russell RK, Gaya DR. The Effects of Commonly Consumed Dietary Fibres on the Gut Microbiome and Its Fibre Fermentative Capacity in Adults with Inflammatory Bowel Disease in Remission. Nutrients 2022; 14:1053. [PMID: 35268028 PMCID: PMC8912623 DOI: 10.3390/nu14051053] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/25/2022] [Accepted: 02/28/2022] [Indexed: 01/04/2023] Open
Abstract
Introduction: It has been suggested that the gut microbiome of patients with inflammatory bowel disease (IBD) is unable to ferment dietary fibre. This project explored the in vitro effect of fibre fermentation on production of short-chain fatty acids (SCFA) and on microbiome composition. Methods: Faecal samples were collected from 40 adults (>16 y) with IBD (n = 20 with Crohn’s disease and n = 20 with ulcerative colitis) in clinical remission and 20 healthy controls (HC). In vitro batch culture fermentations were carried out using as substrates maize starch, apple pectin, raftilose, wheat bran, α cellulose and a mixture of these five fibres. SCFA concentration (umol/g) was quantified with gas chromatography and microbiome was profiled with 16S rRNA sequencing. Results: Fibre fermentation did not correct the baseline microbial dysbiosis or lower diversity seen in either patients with CD or UC. For all fibres, up to 51% of baseline ASVs or genera changed in abundance in HC. In patients with IBD, fermentation of fibre substrates had no effect on species or genera abundance. Production of SCFA varied among the different fibre substrates but this was not different between the two IBD groups and compared to HC after either 5 or 24 h fermentation. Conclusions: Despite extensive microbial dysbiosis, patients with IBD have a similar capacity to ferment fibre and release SCFA as HC. Fibre supplementation alone may be unlikely to restore to a healthy status the compositional shifts characteristic of the IBD microbiome.
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Affiliation(s)
- Konstantinos Gerasimidis
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Ben Nichols
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Mhairi McGowan
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Vaios Svolos
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Rodanthi Papadopoulou
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Margarita Kokkorou
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Martina Rebull
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Teresita Bello Gonzalez
- Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (B.N.); (M.M.); (V.S.); (R.P.); (M.K.); (M.R.); (T.B.G.)
| | - Richard Hansen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow G51 4TF, UK;
| | - Richard Kay Russell
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Edinburgh EH9 1LF, UK;
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Zhang W, Tan B, Deng J, Yang Q, Chi S, Pang A, Xin Y, Liu Y, Zhang H. PRR-Mediated Immune Response and Intestinal Flora Profile in Soybean Meal-Induced Enteritis of Pearl Gentian Groupers, Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂. Front Immunol 2022; 13:814479. [PMID: 35296073 PMCID: PMC8919722 DOI: 10.3389/fimmu.2022.814479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/25/2022] [Indexed: 11/22/2022] Open
Abstract
Pattern recognition receptors (PRRs) can recognize microbial-specific pathogen-associated molecular patterns, initiate signal cascade transduction, activate the expressions of host immunity and proinflammatory genes, and, ultimately, trigger an immune response against identified pathogens. The present study focused on two outcomes of feeding pearl gentian groupers with high levels of soybean meal (SBM): (1) growth performance and (2) the intestinal environment, including tissue structure, flora profile, and immune responses. Some 720 groupers were randomly divided into three groups (n = 4): (1) controls, fed a 50% fish meal feed (FM), (2) with 20% of the FM substituted with SBM (SBM20), and (3) 40% of the FM substituted with SBM (SBM40). The fish were fed these iso-nitrogenous and iso-lipidic diets for 10 weeks. They were kept in containers with 1 m3 of water under natural light and temperature levels. The experimental results demonstrate that the SBM diets significantly degraded growth performance and intestinal physiology. Typical enteritis characteristics and immune fluctuations appeared, as reflected by the enzyme activities of total superoxide dismutase and lysozyme, and the contents of immunoglobulin M, complement 3, and complement 4. 16SrDNA high-throughput sequencing showed that the intestinal flora was significantly affected, with the abundance of harmful bacteria, such as Vibrio and Streptococcus, increasing with dietary SBM level. Based on "3 + 2" full-length transcriptome sequencing, three triggered PRRs were found in the intestine: the RIG-like receptor, NOD-like receptor, and Toll-like receptor signaling pathways. The intestinal flora variations were significantly correlated with the activation of the three PRR signaling pathways by canonical correlation analysis. These culminated in the transcriptome activation of NF-κB, IRFs, and costimulatory molecules, ultimately promoting the expressions of proinflammatory cytokines, interferons (IFNs), chemokines, and other molecules vital to the innate and/or adaptive immune responses. This study provides new information for diagnosing and preventing SBMIE in aquaculture fish.
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Affiliation(s)
- Wei Zhang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Beiping Tan
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Junming Deng
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Qihui Yang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Shuyan Chi
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Aobo Pang
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Yu Xin
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Yu Liu
- Laboratory of Aquatic Animal Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
| | - Haitao Zhang
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, China
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Stallmach A, Grunert P, Stallhofer J, Löffler B, Baier M, Rödel J, Kiehntopf M, Neugebauer S, Pieper DH, Junca H, Tannapfel A, Merkel U, Schumacher U, Breternitz-Gruhne M, Heller T, Schauer A, Hartmann M, Steube A. Transfer of FRozen Encapsulated multi-donor Stool filtrate for active ulcerative Colitis (FRESCO): study protocol for a prospective, multicenter, double-blind, randomized, controlled trial. Trials 2022; 23:173. [PMID: 35193638 PMCID: PMC8861997 DOI: 10.1186/s13063-022-06095-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 02/07/2022] [Indexed: 11/10/2022] Open
Abstract
Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (<0.2 μm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable. Methods Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12. Discussion This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease. Trial registration ClinicalTrials.govNCT03843385. DRKS (Deutsches Register für Klinische Studien) DRKS00020471
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Affiliation(s)
- Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany.
| | - Philip Grunert
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Johannes Stallhofer
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Bettina Löffler
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Michael Baier
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Jürgen Rödel
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Michael Kiehntopf
- Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Jena, Germany
| | - Sophie Neugebauer
- Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Jena, Germany
| | - Dietmar H Pieper
- Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection, Braunschweig, Germany
| | - Howard Junca
- Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection, Braunschweig, Germany
| | | | - Ute Merkel
- Hospital Pharmacy, Jena University Hospital, Jena, Germany
| | - Ulrike Schumacher
- Center for Clinical Studies Jena (ZKS), Jena University Hospital, Jena, Germany
| | | | - Tabitha Heller
- Center for Clinical Studies Jena (ZKS), Jena University Hospital, Jena, Germany
| | - Anja Schauer
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
| | | | - Arndt Steube
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
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Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis. J Clin Med 2022; 11:jcm11041055. [PMID: 35207328 PMCID: PMC8879222 DOI: 10.3390/jcm11041055] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 11/26/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.
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Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther 2022; 7:48. [PMID: 35165272 PMCID: PMC8844085 DOI: 10.1038/s41392-022-00904-4] [Citation(s) in RCA: 819] [Impact Index Per Article: 273.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 01/13/2022] [Accepted: 01/17/2022] [Indexed: 02/08/2023] Open
Abstract
Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.
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Junca H, Pieper DH, Medina E. The emerging potential of microbiome transplantation on human health interventions. Comput Struct Biotechnol J 2022; 20:615-627. [PMID: 35140882 PMCID: PMC8801967 DOI: 10.1016/j.csbj.2022.01.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/06/2022] [Accepted: 01/08/2022] [Indexed: 02/08/2023] Open
Abstract
The human microbiome has been the subject of intense research over the past few decades, in particular as a promising area for new clinical interventions. The microbiota colonizing the different body surfaces are of benefit for multiple physiological and metabolic processes of the human host and increasing evidence suggests an association between disturbances in the composition and functionality of the microbiota and several pathological conditions. This has provided a rationale for beneficial modulation of the microbiome. One approach being explored for modulating the microbiota in diseased individuals is transferring microbiota or microbiota constituents from healthy donors via microbiome transplantation. The great success of fecal microbiome transplantation for the treatment of Clostridioides difficile infections has encouraged the application of this procedure for the treatment of other diseases such as vaginal disorders via transplantation of vaginal microbiota, or of skin pathologies via the transplantation of skin microbiota. Microbiome modulation could even become a novel strategy for improving the efficacy of cancer therapies. This review discusses the principle, advantages and limitations of microbiome transplantation as well as different clinical contexts where microbiome transplantation has been applied.
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Affiliation(s)
- Howard Junca
- Microbial Interactions and Processes Research Group, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
| | - Dietmar H. Pieper
- Microbial Interactions and Processes Research Group, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
| | - Eva Medina
- Infection Immunology Research Group, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
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Lluansí A, Llirós M, Oliver L, Bahí A, Elias-Masiques N, Gonzalez M, Benejam P, Cueva E, Termes M, Ramió-Pujol S, Malagón M, Amoedo J, Serrano M, Busquets D, Torreabla L, Sabat M, Buxó M, Cambra M, Serra-Pagès M, Delgado-Aros S, García-Gil LJ, Elias I, Aldeguer X. In vitro Prebiotic Effect of Bread-Making Process in Inflammatory Bowel Disease Microbiome. Front Microbiol 2021; 12:716307. [PMID: 34707578 PMCID: PMC8543021 DOI: 10.3389/fmicb.2021.716307] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/31/2021] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD), including its two main categories (Crohn's disease and ulcerative colitis), has been linked both to gut microbiota and to diet. Bread is a daily food that has a potential capacity as a prebiotic. Our aim was to evaluate different bread-making processes and their effect on fecal colonic microbiota in IBD patients. The microbial composition of several sourdoughs and dough samples was analyzed by high-throughput sequencing of 16S and 18S rRNA genes. Three types of bread, which followed different bread-making processes, were in vitro digested and incubated with feces from IBD patients. Changes in gut microbiota were assessed by a quantitative polymerase chain reaction using specific bacterial sequence targets. Short-chain fatty acid production was also analyzed by gas chromatography. Lactobacillus sanfranciscensis was the dominant lactic acid bacteria species found in sourdough and bread doughs prepared using sourdough, whereas Saccharomyces cerevisiae was the most dominant yeast in all groups, especially in bread doughs before baking. Differences in microbial composition in raw bread doughs were more related to the type of dough and elaboration than to fermentation time lengths. The analysis of in vitro fecal incubations with bread conditions revealed an increase in most bacterial groups analyzed and short-chain fatty acid production, both in Crohn's disease and ulcerative colitis samples. Most remarkable increases in short-chain fatty acid production mirrored higher abundances of Roseburia species. The potential prebiotic properties observed were mainly obtained when using a high quantity of bread, regardless of bread type. Overall, this study highlights the bacterial dynamics within the bread-making process and the potential prebiotic effect in IBD patients.
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Affiliation(s)
- Aleix Lluansí
- Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona, Salt, Spain
| | - Marc Llirós
- Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona, Salt, Spain
| | | | - Anna Bahí
- Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona, Salt, Spain
| | | | | | | | | | | | | | | | | | | | - David Busquets
- Digestive Service, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain
| | - Leyanira Torreabla
- Digestive Service, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain
| | - Miriam Sabat
- Digestive Service, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain
| | - Maria Buxó
- Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona, Salt, Spain
| | - Maria Cambra
- Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona, Salt, Spain
| | | | | | | | | | - Xavier Aldeguer
- Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona, Salt, Spain.,GoodGut S.L., Girona, Spain.,Digestive Service, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain
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46
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Fan TJ, Goeser L, Lu K, Faith JJ, Hansen JJ. Enterococcus faecalis Glucosamine Metabolism Exacerbates Experimental Colitis. Cell Mol Gastroenterol Hepatol 2021; 12:1373-1389. [PMID: 34246809 PMCID: PMC8479252 DOI: 10.1016/j.jcmgh.2021.06.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 06/18/2021] [Accepted: 06/21/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are caused in part by aberrant immune responses to resident intestinal bacteria. Certain dietary components, including carbohydrates, are associated with IBDs and alter intestinal bacterial composition. However, the effects of luminal carbohydrates on the composition and colitogenic potential of intestinal bacteria are incompletely understood. We hypothesize that carbohydrate metabolism by resident proinflammatory intestinal bacteria enhances their growth and worsens intestinal inflammation. METHODS We colonized germ-free, wild-type, and colitis-susceptible interleukin-10 knockout mice (Il10-/-) with a consortium of resident intestinal bacterial strains and quantified colon inflammation using blinded histologic scoring and spontaneous secretion of IL12/23p40 by colon explants. We measured luminal bacterial composition using real-time 16S polymerase chain reaction, bacterial gene expression using RNA sequencing and real-time polymerase chain reaction, and luminal glucosamine levels using gas chromatography-mass spectrometry. RESULTS We show that a consortium of 8 bacterial strains induces severe colitis in Il10-/- mice and up-regulates genes associated with carbohydrate metabolism during colitis. Specifically, Enterococcus faecalis strain OG1RF is proinflammatory and strongly up-regulates OG1RF_11616-11610, an operon that encodes genes of a previously undescribed phosphotransferase system that we show imports glucosamine. Experimental colitis is associated with increased levels of luminal glucosamine and OG1RF_11616 causes worse colitis, not by increasing E faecalis numbers, but rather by mechanisms that require the presence of complex microbiota. CONCLUSIONS Further studies of luminal carbohydrate levels and bacterial carbohydrate metabolism during intestinal inflammation will improve our understanding of the pathogenesis of IBDs and may lead to the development of novel therapies for these diseases.
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Affiliation(s)
- Ting-Jia Fan
- Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina; Department of Microbiology and Immunology, Chapel Hill, North Carolina
| | - Laura Goeser
- Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina
| | - Kun Lu
- Department of Environmental Sciences and Engineering, Chapel Hill, North Carolina
| | - Jeremiah J Faith
- The Precision Immunology Institute, New York, New York; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jonathan J Hansen
- Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina; Department of Microbiology and Immunology, Chapel Hill, North Carolina; Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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47
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Khanna S. Management of Clostridioides difficile infection in patients with inflammatory bowel disease. Intest Res 2021; 19:265-274. [PMID: 32806873 PMCID: PMC8322030 DOI: 10.5217/ir.2020.00045] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/21/2020] [Accepted: 05/25/2020] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a common diarrheal illness with gastrointestinal and extraintestinal manifestations and complications. The most common infectious complication associated with IBD is Clostridioides difficile infection (CDI). Active IBD predisposes to CDI due to alterations in the gut microbiome. C. difficile is a toxin producing bacterium leading to worsening of underlying IBD, increasing the risk of IBD treatment failure and an increased risk of hospitalization and surgery. Since the symptoms of CDI overlap with those of an IBD flare; it is prudent to recognize that the diagnosis of CDI is challenging and diagnostic tests (nucleic-acid and toxin-based assays) should be interpreted in context of symptoms and test performance. First line treatments for management of CDI in IBD include vancomycin or fidaxomicin. Recurrence prevention strategies should be implemented to mitigate recurrent CDI risk. One needs to monitor IBD disease progression and manage immunosuppression. The risk of recurrent CDI after a primary infection is higher in IBD compared to non-IBD patients. Microbiota restoration therapies are effective to prevent recurrent CDI in IBD patients. This review summarizes the epidemiology, pathophysiology, diagnostic testing, outcomes and management of both CDI and IBD, in CDI complicating IBD.
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Affiliation(s)
- Sahil Khanna
- C. difficile Clinic and Microbial Replacement Therapy Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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48
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Pan G, Liu B, Li S, Han M, Gao L, Xu G, Du Q, Xie L. Kuijieling, a Chinese medicine alleviates DSS-induced colitis in C57BL/6Jmouse by improving the diversity and function of gut microbiota. FEMS Microbiol Lett 2021; 367:5837080. [PMID: 32407465 DOI: 10.1093/femsle/fnaa082] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 05/12/2020] [Indexed: 12/26/2022] Open
Abstract
Ulcerative colitis (UC) is a gastrointestinal disease. The link between gut microbiota and the inflammatory response in the gut has been recently established. Restoration of gut microbiota suppresses inflammatory signaling. Kuijieling (KJL) decoction, an experimental Chinese medicine formula could ameliorate the symptom of colitis. However, the involvement of gut microbiota in its curative effect remains known. Here, we would like to assess the therapeutic effect of KJL in DSS-induced UC model. Mouse feces were collected, followed by 16S rRNA sequencing. Kuijieling decoction improved gut microbial homeostasis and suppressed inflammation in the UC model. A 5-fold cross-validation and random forest analysis identified seven signature bacterial taxa representing the DSS-mediated pathogenic condition and recovery stage upon KJL decoction treatment. Overall, the findings support the notion of KJL decoction-mediated restoration of gut microbiota as a critical step of inducing remission and alleviating UC symptoms. In the present investigation, we aimed to address the question of whether KJL decoction alleviates the UC symptoms by manipulating the gut microbial structure and function.
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Affiliation(s)
- Guihua Pan
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangdong, China
| | - Bingdong Liu
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China
| | - Sixing Li
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangdong, China
| | - Mulan Han
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China
| | - Liang Gao
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China
| | - Guohuan Xu
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China
| | - Qun Du
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangdong, China
| | - Liwei Xie
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China.,Zhujiang Hospital, Southern Medical University, Guangdong 510282, China.,School of Public Health, Xinxiang Medical University, Henan 453003, China
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49
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Li W, Sun Y, Dai L, Chen H, Yi B, Niu J, Wang L, Zhang F, Luo J, Wang K, Guo R, Li L, Zou Q, Ma ZS, Miao Y. Ecological and network analyses identify four microbial species with potential significance for the diagnosis/treatment of ulcerative colitis (UC). BMC Microbiol 2021; 21:138. [PMID: 33947329 PMCID: PMC8097971 DOI: 10.1186/s12866-021-02201-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 04/05/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. RESULTS In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. CONCLUSIONS Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.
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Affiliation(s)
- Wendy Li
- Computational Biology and Medical Ecology Lab, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.,Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Lin Dai
- Faculty of Science, Kunming University of Science and Technology, Kunming, China
| | - Hongju Chen
- Computational Biology and Medical Ecology Lab, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.,Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, China.,College of Mathematics, Honghe University, Mengzi, Yunnan Province, China
| | - Bin Yi
- College of Mathematics, Honghe University, Mengzi, Yunnan Province, China
| | - Junkun Niu
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Lan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Fengrui Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Juan Luo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Kunhua Wang
- Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Rui Guo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China
| | - Lianwei Li
- Computational Biology and Medical Ecology Lab, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.,Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, China
| | - Quan Zou
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhanshan Sam Ma
- Computational Biology and Medical Ecology Lab, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. .,Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, China. .,Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, China.
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50
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Aldars-García L, Chaparro M, Gisbert JP. Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease. Microorganisms 2021; 9:microorganisms9050977. [PMID: 33946482 PMCID: PMC8147118 DOI: 10.3390/microorganisms9050977] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.
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Affiliation(s)
- Laila Aldars-García
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - Javier P. Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
- Correspondence: ; Tel.: +34-913-093-911; Fax: +34-915-204-013
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