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1
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Su F, Su M, Wei W, Wu J, Chen L, Sun X, Liu M, Sun S, Mao R, Bourgonje AR, Hu S. Integrating multi-omics data to reveal the host-microbiota interactome in inflammatory bowel disease. Gut Microbes 2025; 17:2476570. [PMID: 40063366 PMCID: PMC11901428 DOI: 10.1080/19490976.2025.2476570] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/14/2025] [Accepted: 03/03/2025] [Indexed: 03/14/2025] Open
Abstract
Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.
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Affiliation(s)
- Fengyuan Su
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Meng Su
- The First Clinical Medical School, Nanfang Hospital of Southern Medical University, Guangzhou, China
| | - Wenting Wei
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Jiayun Wu
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Leyan Chen
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Xiqiao Sun
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Moyan Liu
- Amsterdam UMC location Academic Medical Center, Department of Experimental Vascular Medicine, Amsterdam, The Netherlands
| | - Shiqiang Sun
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Arno R. Bourgonje
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shixian Hu
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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2
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Koller AM, Săsăran MO, Mărginean CO. Small Intestinal Bacterial Overgrowth and Pediatric Obesity-A Systematic Review. Nutrients 2025; 17:1499. [PMID: 40362809 PMCID: PMC12073544 DOI: 10.3390/nu17091499] [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: 04/01/2025] [Revised: 04/26/2025] [Accepted: 04/26/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: Childhood obesity is a growing global concern linked to metabolic disorders such as nonalcoholic fatty liver disease (NAFLD). Small intestinal bacterial overgrowth (SIBO) may exacerbate these conditions by promoting systemic inflammation and metabolic dysfunction. This review evaluates the prevalence of SIBO in obese children, its association with inflammatory and metabolic markers, and the efficacy of diagnostic and therapeutic strategies. Methods: A systematic search of PubMed, Scopus, and Web of Science (2010-present) was conducted using Boolean operators: ('small intestinal bacterial overgrowth' OR 'SIBO') AND 'prevalence' AND ('low-grade inflammatory markers' OR 'metabolic status') AND 'gut microbiome' AND 'dysbiosis' AND 'obese children'. Results: The data show that SIBO is frequently observed in obese pediatric populations and is associated with gut dysbiosis, impaired nutrient absorption, and reduced production of short-chain fatty acids. These changes contribute to increased intestinal permeability, endotoxemia, and chronic low-grade inflammation. Several microbial taxa have been proposed as biomarkers and therapeutic targets. Diagnostic inconsistencies persist, but treatments such as probiotics, prebiotics, dietary interventions, and selective antibiotics show potential, pending further validation. Conclusions: Early identification and treatment of SIBO with tailored strategies may help reduce metabolic complications and improve outcomes in children with obesity.
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Affiliation(s)
- Ana Maria Koller
- Doctoral School, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Maria Oana Săsăran
- Department of Pediatrics 3, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
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Gold S, Park S, Katz J, McClave S, Martindale R. The Evolving Guidelines on Fiber Intake for Patients with Inflammatory Bowel Disease; From Exclusion to Texture Modification. Curr Gastroenterol Rep 2025; 27:23. [PMID: 40131665 DOI: 10.1007/s11894-025-00975-7] [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] [Accepted: 03/12/2025] [Indexed: 03/27/2025]
Abstract
PURPOSE OF REVIEW Fiber restriction has been a long-standing strategy for patients with inflammatory bowel disease (IBD), ostensibly to improve symptoms and reduce complications. Fiber though has a well-documented trophic effect on gut barrier defenses and the intestinal microbiome. This report discusses how texture modification may allow the safe and effective provision of much needed fiber to this patient population. RECENT FINDINGS The effect of dietary fiber is characterized by maintenance of gut integrity, support of the microbiome, and immune modulation. Low-fiber diets in patients with IBD result in greater dysbiosis, intestinal permeability, and mucosal inflammation. New recommendations from international IBD guidelines now promote texture modification to allow for inclusion of fiber in certain conditions of IBD. For patients flaring with acute inflammation, or those with ileostomy, intestinal stricture, or ileal pouch anastomosis, continued fiber intake with softer textures and mechanical modification should be prioritized when feasible. For patients recovering from surgery, diet advancement should include reintroduction of soluble and insoluble fibers, while those in remission should have little or no dietary restrictions. Texture modification of high fiber foods may be accomplished by a variety of strategies involved in the selection, preparation, and cooking of fruits and vegetables. Greater effort to include dietary soluble and insoluble fiber should result in clinical benefit to the IBD patient, avoiding the adverse consequences of a low-fiber diet.
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Affiliation(s)
- Stephanie Gold
- The Henry d. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
| | - Sunhee Park
- Irvine, School of Medicine, University of California, Orange, CA, USA
| | | | - Stephen McClave
- Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA
| | - Robert Martindale
- Department of Surgery, Oregon Health Sciences University, Portland, OR, USA
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Wang N, Sieng S, Liang T, Chen P, Xu J, Han Q. Effect of Toxocara canis infection on liver and lung microbial flora diversity and composition in dogs. Parasite 2025; 32:17. [PMID: 40043197 PMCID: PMC11882136 DOI: 10.1051/parasite/2025011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 02/13/2025] [Indexed: 05/13/2025] Open
Abstract
Toxocariasis is a zoonotic parasitic disease that is widely prevalent in the world. Toxocara canis adults are parasitic in the small intestinal tract of canids, and the larvae migrate to the liver and lungs before reaching the final destination. Our previous experiments have confirmed that T. canis infection could affect the composition of host intestinal microbial flora. In this experiment, we further analyze the potential effects of T. canis infection on host liver and lung microbial flora. Utilizing 16s rRNA high-throughput sequencing, coupled with various bioinformatics analysis techniques, our study revealed that T. canis infection significantly elevated the abundance of certain opportunistic pathogens in the host's liver and lungs. This marked elevation contributes to the establishment of infection. Through cluster analysis, we found that the changes in the microbiota of the liver and lungs were independent of the microbial flora carried by T. canis adults. However, whether the changes are due to the migration of larvae remains to be explored. In short, T. canis infections have a significant impact on the abundance and diversity of flora in the host tissues, and the changes in microbiota abundance and diversity could further influence tissue homeostasis and immune responses, thus regulating the establishment of infection.
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Affiliation(s)
- Na Wang
- Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Hainan International One Health Institute, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
| | - Soben Sieng
- Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Hainan International One Health Institute, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
| | - Tian Liang
- Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Hainan International One Health Institute, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
| | - Ping Chen
- Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Hainan International One Health Institute, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
| | - Jingyun Xu
- Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Hainan International One Health Institute, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Faculty of Veterinary Medicine, Royal University of Agriculture Dongkor District Phnom Penh 120501 Cambodia
| | - Qian Han
- Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Hainan International One Health Institute, Hainan University 58 Renmin Avenue Haikou 570228 Hainan China
- Faculty of Veterinary Medicine, Royal University of Agriculture Dongkor District Phnom Penh 120501 Cambodia
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5
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Hernández-Rocha C, Turpin W, Borowski K, Stempak JM, Sabic K, Gettler K, Tastad C, Chasteau C, Korie U, Hanna M, Khan A, Mengesha E, Bitton A, Schwartz MB, Barrie A, Datta LW, Lazarev M, Brant SR, Rioux JD, McGovern DPB, Duerr RH, Schumm LP, Cho JH, Silverberg MS. After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence. Clin Gastroenterol Hepatol 2025; 23:612-620.e10. [PMID: 38969076 PMCID: PMC11979954 DOI: 10.1016/j.cgh.2024.06.022] [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: 03/19/2024] [Revised: 06/13/2024] [Accepted: 06/18/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND & AIMS Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. METHODS Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. RESULTS A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. CONCLUSIONS Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.
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Affiliation(s)
- Cristian Hernández-Rocha
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica of Chile, Santiago, Chile
| | - Williams Turpin
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Krzysztof Borowski
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Joanne M Stempak
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Ksenija Sabic
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Kyle Gettler
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Christopher Tastad
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Colleen Chasteau
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ujunwa Korie
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Mary Hanna
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California
| | - Abdul Khan
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California
| | - Emebet Mengesha
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marc B Schwartz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Arthur Barrie
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Lisa W Datta
- Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark Lazarev
- Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Steven R Brant
- Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School and the Crohn's and Colitis Center of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey; Department of Genetics and The Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, New Jersey
| | - John D Rioux
- Research Centre, Montreal Heart Institute, Montréal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Dermot P B McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California
| | - Richard H Duerr
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania
| | - L Phil Schumm
- Biostatistics Laboratory & Research Computing Group, Department of Public Health Sciences, University of Chicago, Chicago, Illinois
| | - Judy H Cho
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Mark S Silverberg
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
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6
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Sun N, Ogulur I, Mitamura Y, Yazici D, Pat Y, Bu X, Li M, Zhu X, Babayev H, Ardicli S, Ardicli O, D'Avino P, Kiykim A, Sokolowska M, van de Veen W, Weidmann L, Akdis D, Ozdemir BG, Brüggen MC, Biedermann L, Straumann A, Kreienbühl A, Guttman-Yassky E, Santos AF, Del Giacco S, Traidl-Hoffmann C, Jackson DJ, Wang DY, Lauerma A, Breiteneder H, Zhang L, O'Mahony L, Pfaar O, O'Hehir R, Eiwegger T, Fokkens WJ, Cabanillas B, Ozdemir C, Kistler W, Bayik M, Nadeau KC, Torres MJ, Akdis M, Jutel M, Agache I, Akdis CA. The epithelial barrier theory and its associated diseases. Allergy 2024; 79:3192-3237. [PMID: 39370939 DOI: 10.1111/all.16318] [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: 05/17/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 10/08/2024]
Abstract
The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.
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Affiliation(s)
- Na Sun
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, P. R. China
| | - Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xiangting Bu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Manru Li
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xueyi Zhu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Huseyn Babayev
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Genetics, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey
| | - Ozge Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Division of Food Processing, Milk and Dairy Products Technology Program, Karacabey Vocational School, Bursa Uludag University, Bursa, Turkey
| | - Paolo D'Avino
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Ayca Kiykim
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Pediatrics, Division of Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Lukas Weidmann
- Department of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Deniz Akdis
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | | | - Marie Charlotte Brüggen
- Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Andrea Kreienbühl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Emma Guttman-Yassky
- Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital, London, UK
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Stefano Del Giacco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | | | - David J Jackson
- Guy's Severe Asthma Centre, Guy's Hospital, Guy's & St Thomas' NHS Trust, London, UK
- School of Immunology & Microbial Sciences, King's College London, London, UK
| | - De-Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore City, Singapore
| | - Antti Lauerma
- Department of Dermatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Heimo Breiteneder
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Liam O'Mahony
- Department of Medicine and School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Oliver Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
| | - Robyn O'Hehir
- Allergy, Asthma & Clinical Immunology, The Alfred Hospital, Melbourne, Victoria, Australia
- Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Thomas Eiwegger
- Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
- Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten, Austria
| | - Wytske J Fokkens
- Department of Otorhinolaryngology & Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Beatriz Cabanillas
- Department of Allergy, Instituto de Investigación Biosanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Cevdet Ozdemir
- Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul University, Istanbul, Turkey
- Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy and Immunology, Istanbul University, Istanbul, Turkey
| | - Walter Kistler
- Department of Sports Medicine, Davos Hospital, Davos, Switzerland
- Swiss Research Institute for Sports Medicine (SRISM), Davos, Switzerland
- Medical Committee International Ice Hockey Federation (IIHF), Zurich, Switzerland
| | - Mahmut Bayik
- Department of Internal Medicine and Hematology, Marmara University, Istanbul, Turkey
| | - Kari C Nadeau
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Maria J Torres
- Allergy Unit, IBIMA-Hospital Regional Universitario de Málaga-ARADyAL, UMA, Málaga, Spain
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Marek Jutel
- Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland
| | - Ioana Agache
- Faculty of Medicine, Department of Allergy and Clinical Immunology, Transylvania University, Brasov, Romania
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
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7
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Ci Y, Ku T, Su Y, He Z, Zhang Y, Ji J, Ning X, Yin S, Zhang K. Response signatures of intestinal microbiota and gene transcription of yellow catfish (Pelteobagrus fulvidraco) to Aeromonas hydrophila infection. FISH & SHELLFISH IMMUNOLOGY 2024; 152:109797. [PMID: 39084276 DOI: 10.1016/j.fsi.2024.109797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/15/2024] [Accepted: 07/28/2024] [Indexed: 08/02/2024]
Abstract
Bacterial intestinal inflammation is a common disease of yellow catfish (Pelteobagrus fulvidraco) in high-density aquaculture. Understanding the interactions between host and intestinal bacteria is helpful to intestinal inflammatory disease control. Here, we constructed a model of intestinal inflammation after Aeromonas hydrophila infection in yellow catfish, and characterized variations in gene expression and microbiome in the gut through high-throughput sequencing. Furthermore, host gene-microbiome interactions were identified. Histology observation showed disordered distribution of columnar epithelial cells and decrease of goblet cells in intestine. A total of 4741 genes showed differentially expression, mostly in comparisons between 12 hpi group with each other groups respectively, including control, 24 hpi and 48 hpi groups. These genes were enriched in immune-related pathways including the IL-17 signaling pathway, triggering strong inflammatory response at the invading stage within 12 h. Subsequently, the host strengthened energy consumption by activating carbohydrate and lipid metabolism pathways to repair the intestinal mucosal immune defense line. In addition, fish with A. hydrophila infection show decreased richness of gut microbial, reduced relative abundance of probiotics including Akkermansia, and elevated pathogenic bacteria such as Plesimonas. An integrative analysis identified A. hydrophila-related genes, such as il22 and stat3, for which expression level is close associated with the shift of A. hydrophila-related bacteria relative abundance, such as Akkermansia and Cetobacterium. Aside from picturing the variations of intestine gene expression and mucosal microbiome of yellow catfish coping with A. hydrophila infection, our study probed the underlying host-microbe interactions in A. hydrophila infection induced intestinal inflammatory, providing new insights for disease control in aquaculture.
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Affiliation(s)
- Yuting Ci
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China
| | - Tinglan Ku
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China
| | - Yiting Su
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China
| | - Zhimin He
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China
| | - Yufei Zhang
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China
| | - Jie Ji
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China; Co-Innovation Center for Marine Bio-Industry Technology, Lian Yungang, Jiangsu, 222005, China
| | - Xianhui Ning
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China; Co-Innovation Center for Marine Bio-Industry Technology, Lian Yungang, Jiangsu, 222005, China
| | - Shaowu Yin
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China; Co-Innovation Center for Marine Bio-Industry Technology, Lian Yungang, Jiangsu, 222005, China
| | - Kai Zhang
- College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing, 210023, China; Co-Innovation Center for Marine Bio-Industry Technology, Lian Yungang, Jiangsu, 222005, China.
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Niu X, Lin L, Zhang T, An X, Li Y, Yu Y, Hong M, Shi H, Ding L. Comparison of the intestinal flora of wild and artificial breeding green turtles ( Chelonia mydas). Front Microbiol 2024; 15:1412015. [PMID: 38873159 PMCID: PMC11170157 DOI: 10.3389/fmicb.2024.1412015] [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: 04/04/2024] [Accepted: 05/06/2024] [Indexed: 06/15/2024] Open
Abstract
Gut microbes are pivotal reference indicators for assessing the health status of animals. Before introducing artificially bred species into the wild, examining their gut microbe composition is crucial to help mitigate potential threats posed to wild populations. However, gut microbiological trait similarities between wild and artificially bred green turtles remain unexplored. Therefore, this study compared the gut microbiological characteristics of wild and artificially bred green turtles (Chelonia mydas) through high-throughput Illumina sequencing technology. The α-diversity of intestinal bacteria in wild green turtles, as determined by Shannon and Chao indices, significantly surpasses that of artificial breeding green turtles (p < 0.01). However, no significant differences were detected in the fungal α-diversity between wild and artificially bred green turtles. Meanwhile, the β-diversity analysis revealed significant differences between wild and artificially bred green turtles in bacterial and fungal compositions. The community of gut bacteria in artificially bred green turtles had a significantly higher abundance of Fusobacteriota including those belonging to the Paracoccus, Cetobacterium, and Fusobacterium genera than that of the wild green turtle. In contrast, the abundance of bacteria belonging to the phylum Actinobacteriota and genus Nautella significantly decreased. Regarding the fungal community, artificially bred green turtles had a significantly higher abundance of Fusarium, Sterigmatomyces, and Acremonium and a lower abundance of Candida and Rhodotorula than the wild green turtle. The PICRUSt2 analyses demonstrated significant differences in the functions of the gut bacterial flora between groups, particularly in carbohydrate and energy metabolism. Fungal functional guild analysis further revealed that the functions of the intestinal fungal flora of wild and artificially bred green turtles differed significantly in terms of animal pathogens-endophytes-lichen parasites-plant pathogens-soil saprotrophs-wood saprotrophs. BugBase analysis revealed significant potential pathogenicity and stress tolerance variations between wild and artificially bred green turtles. Collectively, this study elucidates the distinctive characteristics of gut microbiota in wild and artificially bred green turtles while evaluating their health status. These findings offer valuable scientific insights for releasing artificially bred green turtles and other artificially bred wildlife into natural habitats.
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Affiliation(s)
- Xin Niu
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
| | - Liu Lin
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
| | - Ting Zhang
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
| | - Xiaoyu An
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
| | - Yupei Li
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
- Marine Protected Area Administration of Sansha City, Sansha, China
| | - Yangfei Yu
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
- Marine Protected Area Administration of Sansha City, Sansha, China
| | - Meiling Hong
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
| | - Haitao Shi
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
| | - Li Ding
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, China
- Hainan Sansha Provincial Observation and Research Station of Sea Turtle Ecology, Sansha, China
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Lewis JD, Daniel SG, Li H, Hao F, Patterson AD, Hecht AL, Brensinger CM, Wu GD, Bittinger K. Surgery for Crohn's Disease Is Associated With a Dysbiotic Microbiome and Metabolome: Results From Two Prospective Cohorts. Cell Mol Gastroenterol Hepatol 2024; 18:101357. [PMID: 38750900 PMCID: PMC11278594 DOI: 10.1016/j.jcmgh.2024.05.005] [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: 02/14/2024] [Revised: 05/05/2024] [Accepted: 05/07/2024] [Indexed: 06/19/2024]
Abstract
BACKGROUND & AIMS Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, Egerthella lenta, Adlercreutzia equalofaciens, and Gordonibacter pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS In 2 different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria and secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.
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Affiliation(s)
- James D Lewis
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Scott G Daniel
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Hongzhe Li
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Fuhua Hao
- Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, State College, Pennsylvania
| | - Andrew D Patterson
- Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, State College, Pennsylvania
| | - Aaron L Hecht
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Colleen M Brensinger
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Gary D Wu
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kyle Bittinger
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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10
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Wang H, Yan G, Wu Y, Zhuoma D, Liu Z, Gao X, Wang X. Fecal microbiota related to postoperative endoscopic recurrence in patients with Crohn's disease. Gastroenterol Rep (Oxf) 2024; 12:goae017. [PMID: 38524186 PMCID: PMC10960934 DOI: 10.1093/gastro/goae017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 11/05/2023] [Accepted: 02/26/2024] [Indexed: 03/26/2024] Open
Abstract
Background Postoperative recurrence (POR) remains a major challenge for patients with Crohn's disease (CD). Gut microbial dysbiosis has been reported to be involved in the pathogenesis of POR. This study aims to investigate the relationship between fecal microbiome and endoscopic recurrence in patients with CD after ileocolonic resection. Methods This is a cross-sectional study. Fecal samples were collected from 52 patients with CD after surgical intervention from 6 to 12 months before endoscopic examination. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. The microbiome was analyzed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Results A total of 52 patients were included and classified into POR (n = 27) and non-POR (n = 25) groups. Compared with the non-POR group, the POR group had a significantly lower community richness (Chao1 index: 106.5 vs 124, P = 0.013) and separated microbial community (P = 0.007 for Adonis, P = 0.032 for Anosim), combined with different distribution of 16 gut microbiotas and decrease of 11 predicted metabolic pathways (P < 0.05). Lactobacillus and Streptococcus were identified to closely correlate to non-POR (P < 0.05) after controlling for confounding factors. Kaplan-Meier analysis indicated that the patients with higher abundance of Streptococcus experienced longer remission periods (P < 0.01), but this was not for Lactobacillus. The predicted ethylmalonyl-coA pathway related to increased amount of succinate was positively correlated with Streptococcus (r > 0.5, P < 0.05). Conclusions The characteristic alterations of fecal microbiota are associated with postoperative endoscopic recurrence in patients with CD; particularly, high abundance of Streptococcus may be closely related to endoscopic remission.
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Affiliation(s)
- Haichao Wang
- Department of Nephrology and Rheumatology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, P. R. China
| | - Guorong Yan
- Department of Phototherapy, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, P. R. China
| | - Yaling Wu
- Department of Geriatrics, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, P. R. China
| | - Deji Zhuoma
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, P. R. China
| | - Zhanju Liu
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, P. R. China
| | - Xuefeng Gao
- Integrative Microecology Center, Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, P. R. China
| | - Xiaolei Wang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, P. R. China
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11
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Tsigalou C, Paraschaki A, Bragazzi NL, Aftzoglou K, Stavropoulou E, Tsakris Z, Vradelis S, Bezirtzoglou E. Alterations of gut microbiome following gastrointestinal surgical procedures and their potential complications. Front Cell Infect Microbiol 2023; 13:1191126. [PMID: 37333847 PMCID: PMC10272562 DOI: 10.3389/fcimb.2023.1191126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023] Open
Abstract
Intestinal microorganisms play a crucial role in shaping the host immunity and maintaining homeostasis. Nevertheless, alterations in gut bacterial composition may occur and these alterations have been linked with the pathogenesis of several diseases. In surgical practice, studies revealed that the microbiome of patients undergoing surgery changes and several post-operative complications seem to be associated with the gut microbiota composition. In this review, we aim to provide an overview of gut microbiota (GM) in surgical disease. We refer to several studies which describe alterations of GM in patients undergoing different types of surgery, we focus on the impacts of peri-operative interventions on GM and the role of GM in development of post-operative complications, such as anastomotic leak. The review aims to enhance comprehension regarding the correlation between GM and surgical procedures based in the current knowledge. However, preoperative and postoperative synthesis of GM needs to be further examined in future studies, so that GM-targeted measures could be assessed and the different surgery complications could be reduced.
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Affiliation(s)
- Christina Tsigalou
- Laboratory of Microbiology, Faculty of Medicine, Democritus University of Thrace, Dragana Campus, Alexandroupolis, Greece
| | - Afroditi Paraschaki
- Department of Biopathology/Microbiology, Faculty of Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Nicola Luigi Bragazzi
- Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada
| | - K. Aftzoglou
- Medical School, Comenius University, Bratislava, Slovakia
| | - Elisavet Stavropoulou
- Department of Infectious Diseases, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon, Lausanne, Switzerland
| | - Z. Tsakris
- Laboratory of Microbiology, Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - S. Vradelis
- Department of Gastrenterology, Faculty of Medicine, Democritus University of Thrace, Dragana Campus, Alexandroupolis, Greece
| | - Eugenia Bezirtzoglou
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana, Alexandroupolis, Greece
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Baslam A, Aitbaba A, Lamrani Hanchi A, Tazart Z, Aboufatima R, Soraa N, Ait-El-Mokhtar M, Boussaa S, Baslam M, Chait A. Modulation of Gut Microbiome in Ecstasy/MDMA-Induced Behavioral and Biochemical Impairment in Rats and Potential of Post-Treatment with Anacyclus pyrethrum L. Aqueous Extract to Mitigate Adverse Effects. Int J Mol Sci 2023; 24:ijms24109086. [PMID: 37240429 DOI: 10.3390/ijms24109086] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/16/2023] [Accepted: 05/20/2023] [Indexed: 05/28/2023] Open
Abstract
The use of illicit substances continues to pose a substantial threat to global health, affecting millions of individuals annually. Evidence suggests the existence of a 'brain-gut axis' as the involving connection between the central nervous system and gut microbiome (GM). Dysbiosis of the GM has been associated with the pathogenesis of various chronic diseases, including metabolic, malignant, and inflammatory conditions. However, little is currently known about the involvement of this axis in modulating the GM in response to psychoactive substances. In this study, we investigated the effect of MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy")-dependence on the behavioral and biochemical responses, and the diversity and abundance of the gut microbiome in rats post-treated (or not) with aqueous extract of Anacyclus pyrethrum (AEAP), which has been reported to exhibit anticonvulsant activity. The dependency was validated using the conditioned place preference (CPP) paradigm, behavioral, and biochemical tests, while the gut microbiota was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The CPP and behavioral tests confirmed the presence of MDMA withdrawal syndrome. Interestingly, treatment with AEAP led to a compositional shift in the GM compared to the MDMA-treated rats. Specifically, the AEAP group yielded a higher relative abundance of Lactobacillus and Bifidobacter, while animals receiving MDMA had higher levels of E. coli. These findings suggest that A. pyrethrum therapy may directly modulate the gut microbiome, highlighting a potential target for regulating and treating substance use disorders.
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Affiliation(s)
- Abdelmounaim Baslam
- Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Abdelfatah Aitbaba
- Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Asmae Lamrani Hanchi
- Laboratory of Microbiology, University Hospital Mohamed VI, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Zakaria Tazart
- Department of Food Sciences and Nutrition, Faculty of Health Sciences, University of Malta, Msida 2080, Malta
| | - Rachida Aboufatima
- Laboratory of Biological Engineering, Faculty of Sciences and Technology, Sultan Moulay Slimane University, Beni Mellal 23000, Morocco
| | - Nabila Soraa
- Laboratory of Microbiology, University Hospital Mohamed VI, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Mohamed Ait-El-Mokhtar
- Laboratory of Biochemistry, Environment & Agri-Food URAC 36, Department of Biology, Faculty of Science and Techniques-Mohammedia, Hassan II University of Casablanca, Mohammedia 20000, Morocco
| | - Samia Boussaa
- ISPITS-Higher Institute of Nursing and Health Techniques, Ministry of Health and Social Protection, Rabat 10000, Morocco
| | - Marouane Baslam
- Laboratory of Biochemistry, Department of Applied Biological Chemistry, Faculty of Agriculture, University of Niigata, Niigata 950-2181, Japan
- Centre d'Agrobiotechnologie et Bioingénierie, Unité de Recherche Labellisée CNRST (Centre AgroBiotech-URL-CNRST-05), Université Cadi Ayyad, Marrakesh 40000, Morocco
- Laboratory of Agro-Food, Biotechnologies and Valorization of Plant Bioresources (AGROBIOVAL), Department of Biology, Faculty of Science Semlalia, Cadi Ayyad University (UCA), Marrakesh 40000, Morocco
| | - Abderrahman Chait
- Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco
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Oliver L, Camps B, Julià-Bergkvist D, Amoedo J, Ramió-Pujol S, Malagón M, Bahí A, Torres P, Domènech E, Guardiola J, Serra-Pagès M, Garcia-Gil J, Aldeguer X. Definition of a microbial signature as a predictor of endoscopic post-surgical recurrence in patients with Crohn's disease. FRONTIERS IN MOLECULAR MEDICINE 2023; 3:1046414. [PMID: 39086694 PMCID: PMC11285546 DOI: 10.3389/fmmed.2023.1046414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 01/23/2023] [Indexed: 08/02/2024]
Abstract
Background and aims: Although there are several effective drugs for the treatment of Crohn's disease (CD), almost 70% of patients will require surgical resection during their lifetime. This procedure is not always curative, as endoscopic recurrence occurs in 65%-90% of patients in the first year after surgery. The aetiology of the recurrence is unknown; however, several studies have shown how the resident microbiota is modified after surgery. The aim of this study was to evaluate samples from patients with Crohn's disease before and after an intestinal resection to determine whether there were differences in the abundance of different microbial markers, which may predict endoscopic recurrence at baseline. Methods: In this observational study, a stool sample was obtained from 25 patients with Crohn's disease before undergoing surgery, recruited at three Catalan hospitals. From each sample, DNA was purified and the relative abundance of nine microbial markers was quantified using qPCR. Results: An algorithm composed of four microbial markers (E. coli, F. prausnitzii phylogroup I, Bacteroidetes, and Eubacteria) showed a sensitivity and specificity of 90.91% and 85.71%, respectively, and a positive and negative predictive value of 83.33% and 92.31%, respectively. Conclusion: A microbial signature to determine patients who will have post-surgical recurrence was identified. This tool might be very useful in daily clinical practice, allowing the scheduling of personalized therapy and enabling preventive treatment only in patients who really require it.
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Affiliation(s)
| | - Blau Camps
- Hospital Universitari de Bellvitge, l’Hospitalet de Llobregat, Barcelona, Spain
| | | | | | | | | | - Anna Bahí
- Institut d’Investigació Biomèdica de Girona—IdIBGi Girona, Girona, Spain
| | - Paola Torres
- Hospital Germans Tries i Pujol, CIBEREHD Badalona, Badalona, Spain
| | - Eugeni Domènech
- Hospital Germans Tries i Pujol, CIBEREHD Badalona, Badalona, Spain
| | - Jordi Guardiola
- Hospital Universitari de Bellvitge, l’Hospitalet de Llobregat, Barcelona, Spain
| | | | - Jesus Garcia-Gil
- GoodGut S.L.U, Girona, Spain
- Biology Department, University of Girona, Girona, Spain
| | - Xavier Aldeguer
- GoodGut S.L.U, Girona, Spain
- Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain
- Institut d’Investigació Biomèdica de Girona—IdIBGi Girona, Girona, Spain
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14
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Ribeiro BE, Breves J, de Souza HSP. Pathogenesis: Crohn’s disease and ulcerative colitis. NATURAL PLANT PRODUCTS IN INFLAMMATORY BOWEL DISEASES 2023:9-46. [DOI: 10.1016/b978-0-323-99111-7.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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15
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Gibiino G, Binda C, Cristofaro L, Sbrancia M, Coluccio C, Petraroli C, Jung CFM, Cucchetti A, Cavaliere D, Ercolani G, Sambri V, Fabbri C. Dysbiosis and Gastrointestinal Surgery: Current Insights and Future Research. Biomedicines 2022; 10:2532. [PMID: 36289792 PMCID: PMC9599064 DOI: 10.3390/biomedicines10102532] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/02/2022] [Accepted: 10/03/2022] [Indexed: 11/16/2022] Open
Abstract
Surgery of the gastrointestinal tract can result in deep changes among the gut commensals in terms of abundance, function and health consequences. Elective colorectal surgery can occur for neoplastic or inflammatory bowel disease; in these settings, microbiota imbalance is described as a preoperative condition, and it is linked to post-operative complications, as well. The study of bariatric patients led to several insights into the role of gut microbiota in obesity and after major surgical injuries. Preoperative dysbiosis and post-surgical microbiota reassessment are still poorly understood, and they could become a key part of preventing post-surgical complications. In the current review, we outline the most recent literature regarding agents and molecular pathways involved in pre- and post-operative dysbiosis in patients undergoing gastrointestinal surgery. Defining the standard method for microbiota assessment in these patients could set up the future approach and clinical practice.
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Affiliation(s)
- Giulia Gibiino
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Cecilia Binda
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Ludovica Cristofaro
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
| | - Monica Sbrancia
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Chiara Coluccio
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Chiara Petraroli
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Carlo Felix Maria Jung
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì-Cesena, Italy
| | - Davide Cavaliere
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì-Cesena, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì-Cesena, Italy
| | - Vittorio Sambri
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
- Microbiology Unit, Hub Laboratory, AUSL della Romagna, 47121 Forlì-Cesena, Italy
| | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
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16
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Battat R, Sandborn WJ. Advances in the Comprehensive Management of Postoperative Crohn's Disease. Clin Gastroenterol Hepatol 2022; 20:1436-1449. [PMID: 33819666 DOI: 10.1016/j.cgh.2021.03.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/21/2021] [Accepted: 03/30/2021] [Indexed: 02/06/2023]
Abstract
Patients with postoperative Crohn's disease are difficult to manage because of their risk of experiencing a more severe course, multiple symptom confounders, and poor sensitivity of symptomatic remission to rule out intestinal inflammation. In this group, data are lacking on biologic therapeutic efficacy, and recommendations are lacking for those with multiple medication failures. Novel noninvasive testing can simultaneously exclude alternate causes of symptoms (serum C4, fecal fat, small intestinal bowel overgrowth breath testing) and assess intestinal inflammation (fecal calprotectin, endoscopic healing index). In addition, endoscopy-based disease activity assessment and management are required. Endoscopy should be performed within 6 months of surgery, and aggressive disease activity monitoring can be considered with colonoscopy every 1-2 years subsequently to ensure late recurrence is detected. Patients with multiple resections should be screened for short bowel syndrome. Predictive biomarkers are needed to guide medication selection in this high-risk population. Postoperative prophylactic biologic therapy is prudent for patients with preoperative biologic failure. However, there are no high-quality data to guide which agent should be selected. Selecting biologics with an alternative mechanism of action in those who had failed a biologic with adequate drug concentrations and selection of different agents in those with previous intolerance are reasonable. Significantly more study is required to assess the efficacy of therapies in this setting.
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Affiliation(s)
- Robert Battat
- Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York.
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
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17
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Santana PT, Rosas SLB, Ribeiro BE, Marinho Y, de Souza HSP. Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets. Int J Mol Sci 2022; 23:3464. [PMID: 35408838 PMCID: PMC8998182 DOI: 10.3390/ijms23073464] [Citation(s) in RCA: 135] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/17/2022] [Accepted: 03/21/2022] [Indexed: 12/12/2022] Open
Abstract
Microbe-host communication is essential to maintain vital functions of a healthy host, and its disruption has been associated with several diseases, including Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD). Although individual members of the intestinal microbiota have been associated with experimental IBD, identifying microorganisms that affect disease susceptibility and phenotypes in humans remains a considerable challenge. Currently, the lack of a definition between what is healthy and what is a dysbiotic gut microbiome limits research. Nevertheless, although clear proof-of-concept of causality is still lacking, there is an increasingly evident need to understand the microbial basis of IBD at the microbial strain, genomic, epigenomic, and functional levels and in specific clinical contexts. Recent information on the role of diet and novel environmental risk factors affecting the gut microbiome has direct implications for the immune response that impacts the development of IBD. The complexity of IBD pathogenesis, involving multiple distinct elements, suggests the need for an integrative approach, likely utilizing computational modeling of molecular datasets to identify more specific therapeutic targets.
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Affiliation(s)
- Patricia Teixeira Santana
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Siane Lopes Bittencourt Rosas
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Beatriz Elias Ribeiro
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Ygor Marinho
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Heitor S. P. de Souza
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
- D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro 22281-100, RJ, Brazil
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18
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Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn's Disease. Can J Gastroenterol Hepatol 2022; 2022:8416578. [PMID: 35360442 PMCID: PMC8964223 DOI: 10.1155/2022/8416578] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 03/05/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Bile acids help maintain the physiological balance of the gut microbiome and the integrity of the intestinal epithelial barrier. Similarly, intestinal bacteria play a major role in bile acid metabolism as they are involved in crucial biotransformation steps in the enterohepatic circulation pathway. Understanding the relationship between bile acid signalling and the gut microbiome in Crohn's disease can help target new and innovative treatment strategies. AIMS This review summarises the relationship between bile acids and the microbiome in Crohn's disease and discusses potential novel therapeutic options. METHODS We performed a literature review on bile acid signalling, its effect on the gut microbiome, and therapeutic applications in Crohn's disease. RESULTS Current research suggests that there is a strong interplay between the dysregulated microbiota, bile acid metabolism, and the mucosal immune system that can result in a changed immunological function, triggering the inflammatory response in Crohn's disease. Recent studies have demonstrated an association with altering the enterohepatic circulation and activating the farnesoid X receptor signalling pathway with the use of probiotics and faecal microbial transplantation, respectively. Bile acid sequestrants have been shown to have anti-inflammatory, cytoprotective, and anti-apoptotic properties with the potential to alter the intestinal microbial composition, suggesting a possible role in inducing and maintaining Crohn's disease. CONCLUSIONS Active Crohn's disease has been correlated with changes in bacterial concentrations, which may be associated with changes in bile acid modification. Further research should focus on targeting these areas for future therapeutic options.
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19
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Otten AT, Bourgonje AR, Peters V, Alizadeh BZ, Dijkstra G, Harmsen HJM. Vitamin C Supplementation in Healthy Individuals Leads to Shifts of Bacterial Populations in the Gut-A Pilot Study. Antioxidants (Basel) 2021; 10:antiox10081278. [PMID: 34439526 PMCID: PMC8389205 DOI: 10.3390/antiox10081278] [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: 07/05/2021] [Revised: 08/06/2021] [Accepted: 08/10/2021] [Indexed: 12/12/2022] Open
Abstract
Gut microbes are crucial to human health, but microbial composition is often disturbed in a number of human diseases. Accumulating evidence points to nutritional modulation of the gut microbiota as a potentially beneficial therapeutic strategy. Vitamin C (ascorbic acid) may be of particular interest as it has known antioxidant and anti-inflammatory properties. In this study, we investigated whether supplementation with high-dose vitamin C may favourably affect the composition of the gut microbiota. In this pilot study, healthy human participants received 1000 mg vitamin C supplementation daily for two weeks. Gut microbiota composition was analysed before and after intervention by performing faecal 16S rRNA gene sequencing. In total, 14 healthy participants were included. Daily supplementation of high-dose vitamin C led to an increase in the relative abundances of Lachnospiraceae (p < 0.05), whereas decreases were observed for Bacteroidetes (p < 0.01), Enterococci (p < 0.01) and Gemmiger formicilis (p < 0.05). In addition, trends for bacterial shifts were observed for Blautia (increase) and Streptococcus thermophilus (decrease). High-dose vitamin C supplementation for two weeks shows microbiota-modulating effects in healthy individuals, with several beneficial shifts of bacterial populations. This may be relevant as these bacteria have anti-inflammatory properties and strongly associate with gut health.
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Affiliation(s)
- Antonius T. Otten
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (A.T.O.); (A.R.B.); (V.P.); (G.D.)
| | - Arno R. Bourgonje
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (A.T.O.); (A.R.B.); (V.P.); (G.D.)
| | - Vera Peters
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (A.T.O.); (A.R.B.); (V.P.); (G.D.)
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands;
| | - Behrooz Z. Alizadeh
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands;
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (A.T.O.); (A.R.B.); (V.P.); (G.D.)
| | - Hermie J. M. Harmsen
- Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
- Correspondence: ; Tel.: +31-50-361-3480
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20
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The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases. Microorganisms 2021; 9:microorganisms9040697. [PMID: 33801755 PMCID: PMC8066304 DOI: 10.3390/microorganisms9040697] [Citation(s) in RCA: 162] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.
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21
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Clooney AG, Eckenberger J, Laserna-Mendieta E, Sexton KA, Bernstein MT, Vagianos K, Sargent M, Ryan FJ, Moran C, Sheehan D, Sleator RD, Targownik LE, Bernstein CN, Shanahan F, Claesson MJ. Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study. Gut 2021; 70:499-510. [PMID: 32536605 PMCID: PMC7873428 DOI: 10.1136/gutjnl-2020-321106] [Citation(s) in RCA: 146] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 05/12/2020] [Accepted: 05/14/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. DESIGN Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn's disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals). RESULTS Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained. CONCLUSION The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.
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Affiliation(s)
- Adam G Clooney
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Julia Eckenberger
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Emilio Laserna-Mendieta
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Kathryn A Sexton
- The University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Matthew T Bernstein
- The University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Kathy Vagianos
- The University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Michael Sargent
- The University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada
- Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Feargal J Ryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Carthage Moran
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Medicine, University College, Cork, Ireland
| | - Donal Sheehan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Medicine, University College, Cork, Ireland
| | - Roy D Sleator
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Biological Sciences, Cork Institute of Technology, Cork, Ireland
| | - Laura E Targownik
- The University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada
- Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Charles N Bernstein
- The University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada
- Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Fergus Shanahan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Medicine, University College, Cork, Ireland
| | - Marcus J Claesson
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
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22
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Zhuang X, Tian Z, Li N, Mao R, Li X, Zhao M, Xiong S, Zeng Z, Feng R, Chen M. Gut Microbiota Profiles and Microbial-Based Therapies in Post-operative Crohn's Disease: A Systematic Review. Front Med (Lausanne) 2021; 7:615858. [PMID: 33585513 PMCID: PMC7876235 DOI: 10.3389/fmed.2020.615858] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 12/14/2020] [Indexed: 12/19/2022] Open
Abstract
Background and Aims: Gut microbiota recolonization after intestinal resection had been reported to be associated with post-operative recurrence in Crohn's disease (CD). However, the results of different studies are inconsistent and even contradictory. In addition, knowledge on the efficacy of microbial-based therapies in preventing post-operative recurrence of CD is limited. Therefore, the aim of this review was to investigate gut microbiota profiles in patients with CD before and after surgery and evaluate microbial-based therapies in preventing post-operative recurrence. Methods: Electronic databases were searched from inception to 31 June 2020 using predefined terms. Studies that investigated gut microbiota pre- and post-intestinal resection, and microbial-based therapies in preventing post-operative recurrence, were eligible. Study quality was assessed using either the Newcastle-Ottawa scale or Jadad scoring system. Results: Twelve studies investigating gut microbiota of CD patients suffering from operation, and other 12 studies evaluating the efficacy of antibiotics and probiotics, were included in our review. The mucosa-associated microbiota in surgical biopsy of CD patients is significantly distinct from that in normal mucosa from healthy subjects. Gut microbiota recolonization following surgery might be associated with post-operative recurrence in CD patients. Furthermore, CD patients with post-operative recurrence presented a gain in pro-inflammatory pathogenic bacteria and a loss in short-chain fatty acid-producing bacteria before and after surgery. However, no consistent bacteria or metabolites were found to predict the post-operative recurrence of CD. Additionally, microbial-based therapies are deficient and present restricted widespread clinical utility due to several deficiencies. Conclusion: Recurrence-associated bacteria observed pre- and post- operation might be promising in preventing the post-operative recurrence of CD. Furthermore, potential microbe biomarkers for predicting subsequent disease recurrence should be validated with larger sample sizes using more rigorous and standardized methodologies.
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Affiliation(s)
- Xiaojun Zhuang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhenyi Tian
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Na Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaozhi Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Min Zhao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shanshan Xiong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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23
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Ferrie S, Webster A, Wu B, Tan C, Carey S. Gastrointestinal surgery and the gut microbiome: a systematic literature review. Eur J Clin Nutr 2021; 75:12-25. [PMID: 32661352 DOI: 10.1038/s41430-020-0681-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 06/09/2020] [Accepted: 07/01/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES The impact of gastrointestinal surgery on the profile of the human gut microbiome is not fully understood. This review aimed to identify whether there is a change to the profile of the gut microbiome as a result of gastrointestinal surgery. SUBJECTS/METHODS In August 2018, a systematic literature search was conducted in Medline, PreMedline, Embase, CINAHL and The Cochrane Register of Clinical Trials, identifying and critically appraising studies which investigated changes to gut microbiome pre- and post-gastrointestinal surgery. RESULTS Of 2512 results, 14 studies were included for analysis. All studies reported post-surgical change to the microbiome. In 9 of the 14 studies, prevalence of specific bacteria had significantly changed after surgery. Improved outcome was associated with higher levels of beneficial bacteria and greater microbiome diversity post-surgery. CONCLUSION There were methodological limitations in the included studies leading to uncertainty regarding the impact of gastrointestinal surgery alone on the microbiome profile. An ideal future model for research should encompass case-controlled or cohort design with longer term follow-up in a homogeneous patient group. Future research should seek to clarify the gold standard testing method and standardised timing for post-surgical microbiome sample collection. It is imperative that controls for confounders be put in place to attempt to identify the true association between gastrointestinal surgery and changes to gut microbiome.
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Affiliation(s)
- Suzie Ferrie
- University of Sydney, Sydney, NSW, Australia
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Amy Webster
- University of Sydney, Sydney, NSW, Australia
| | - Betty Wu
- St George Hospital, Sydney, NSW, Australia
| | - Charis Tan
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Sharon Carey
- University of Sydney, Sydney, NSW, Australia.
- Royal Prince Alfred Hospital, Sydney, NSW, Australia.
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24
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Hamilton AL, Kamm MA, De Cruz P, Wright EK, Feng H, Wagner J, Sung JJY, Kirkwood CD, Inouye M, Teo SM. Luminal microbiota related to Crohn's disease recurrence after surgery. Gut Microbes 2020; 11:1713-1728. [PMID: 32564657 PMCID: PMC7524166 DOI: 10.1080/19490976.2020.1778262] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Microbial factors are likely to be involved in the recurrence of Crohn's disease (CD) after bowel resection. We investigated the luminal microbiota before and longitudinally after surgery, in relation to disease recurrence, using 16S metagenomic techniques. METHODS In the prospective Post-Operative Crohn's Endoscopic Recurrence (POCER) study, fecal samples were obtained before surgery and 6, 12, and 18 months after surgery from 130 CD patients. Endoscopy was undertaken to detect disease recurrence, defined as Rutgeerts score ≥i2, at 6 months in two-thirds of patients and all patients at 18 months after surgery. The V2 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Cluster analysis was performed at family level, assessing microbiome community differences between patients with and without recurrence. RESULTS Six microbial cluster groups were identified. The cluster associated with maintenance of remission was enriched for the Lachnospiraceae family [adjusted OR 0.47 (0.27-0.82), P = .007]. The OTU diversity of Lachnospiraceae within this cluster was significantly greater than in all other clusters. The cluster enriched for Enterobacteriaceae was associated with an increased risk of disease recurrence [adjusted OR 6.35 (1.24-32.44), P = .026]. OTU diversity of Enterobacteriaceae within this cluster was significantly greater than in other clusters. CONCLUSIONS Luminal bacterial communities are associated with protection from, and the occurrence of, Crohn's disease recurrence after surgery. Recurrence may relate to a higher abundance of facultatively anaerobic pathobionts from the Enterobacteriaceae family. The ecologic change of depleted Lachnospiraceae, a genus of butyrate-producing bacteria, may permit expansion of Enterobacteriaceae through luminal environmental perturbation.
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Affiliation(s)
- Amy L. Hamilton
- Department of Gastroenterology, St Vincent’s Hospital and Department of Medicine, University of Melbourne, Melbourne, Australia
| | - Michael A. Kamm
- Department of Gastroenterology, St Vincent’s Hospital and Department of Medicine, University of Melbourne, Melbourne, Australia,CONTACT Michael A. Kamm St Vincent’s Hospital, Melbourne, Australia
| | - Peter De Cruz
- Department of Gastroenterology, St Vincent’s Hospital and Department of Medicine, University of Melbourne, Melbourne, Australia,Department of Gastroenterology, Austin Health, Melbourne, Australia
| | - Emily K. Wright
- Department of Gastroenterology, St Vincent’s Hospital and Department of Medicine, University of Melbourne, Melbourne, Australia
| | - Hai Feng
- The Chinese University of Hong Kong, Hong Kong, China,Enteric Virus Group, Murdoch Children’s Research Institute, Melbourne, Australia,School of Pharmacy, Harbin Medical University, Harbin, China
| | - Josef Wagner
- Enteric Virus Group, Murdoch Children’s Research Institute, Melbourne, Australia,Peter Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, Melbourne, Australia
| | | | - Carl D. Kirkwood
- Enteric Virus Group, Murdoch Children’s Research Institute, Melbourne, Australia,Enteric and Diarrheal Diseases Global Health, Bill and Melinda Gates Foundation, SeattleUSA, WA, USA
| | - Michael Inouye
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia and Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Shu-Mei Teo
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia and Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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25
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Wang Y, Ding Y, Deng Y, Zheng Y, Wang S. Role of myeloid-derived suppressor cells in the promotion and immunotherapy of colitis-associated cancer. J Immunother Cancer 2020; 8:jitc-2020-000609. [PMID: 33051339 PMCID: PMC7555106 DOI: 10.1136/jitc-2020-000609] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2020] [Indexed: 12/11/2022] Open
Abstract
Colitis-associated cancer (CAC) is a specific type of colorectal cancer that develops from inflammatory bowel disease (IBD). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are essential for the pathological processes of inflammation and cancer. Accumulating evidence indicates that MDSCs play different but vital roles during IBD and CAC development and impede CAC immunotherapy. New insights into the regulatory network of MDSCs in the CAC pathogenesis are opening new avenues for developing strategies to enhance the effectiveness of CAC treatment. In this review, we explore the role of MDSCs in chronic inflammation, dysplasia and CAC and summarize the potential CAC therapeutic strategies based on MDSC blockade.
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Affiliation(s)
- Yungang Wang
- Department of Laboratory Medicine, The First People's Hospital of Yancheng, Nanjing University Medical School, Yancheng, China
| | - Yanxia Ding
- Department of Dermatology, The First People's Hospital of Yancheng, Nanjing University Medical School, Yancheng, China
| | - Yijun Deng
- Department of Critical Care Medicine, The First People's Hospital of Yancheng, Nanjing University Medical School, Yancheng, China
| | - Yu Zheng
- Department of Laboratory Medicine, The First People's Hospital of Yancheng, Nanjing University Medical School, Yancheng, China
| | - Shengjun Wang
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
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Zhu Y, Luo J, Yang Z, Miao Y. High-throughput sequencing analysis of differences in intestinal microflora between ulcerative colitis patients with different glucocorticoid response types. Genes Genomics 2020; 42:1197-1206. [PMID: 32844358 DOI: 10.1007/s13258-020-00986-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 08/12/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Previous investigations reported that the imbalance of intestinal microflora may be the initiation and promotion factor in the pathogenesis of inflammatory bowel disease such as ulcerative colitis (UC). Glucocorticoid is a very important class of regulatory molecules in the body. The response of different individuals to glucocorticoids can be divided into glucocorticoid sensitive, glucocorticoid resistance and glucocorticoid dependence. OBJECTIVE We aimed to investigate the differences in intestinal microflora composition and related metabolic pathways in UC patients with these three different glucocorticoid response types. METHODS The whole genomic DNA was extracted from fecal specimens. High-throughput sequencing technology was used to analyze the fecal 16S rRNA genome of UC patients with different glucocorticoid response types, and functional prediction was performed by PICRUSTs software. RESULTS The results showed that the intestinal microflora of the three groups were mainly composed of Firmicutes, Proteobacteria and Bacteroidetes. Although the species abundance and diversity of intestinal microflora in UC patients differed little among the three groups, the composition of intestinal microflora showed significant heterogeneity, which directly led to differences in the function of intestinal microbiota of UC patients with different glucocorticoid responses. Furthermore, of the 240 pathways, "PANTO-PWY: phosphopantothenate biosynthesis I", "COA-PWY-1: coenzyme A biosynthesis II (mammalian)" and "PWY-4242: pantothenate and coenzyme A biosynthesis III" were significantly different in the three groups. CONCLUSIONS These results indicate that UC patients with different glucocorticoids response types have different bacterial compositions and functions, which lays a foundation for further study of glucocorticoid resistance in UC patients.
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Affiliation(s)
- Yunzhen Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People's Republic of China
| | - Juan Luo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People's Republic of China
| | - Zhaoqing Yang
- Department of Pathogen Biology and Immunology, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Kunming, 650500, People's Republic of China.
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People's Republic of China.
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Bertges ER, Chebli JMF. PREVALENCE AND FACTORS ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH IN PATIENTS WITH CROHN'S DISEASE: A RETROSPECTIVE STUDY AT A REFERRAL CENTER. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:283-288. [PMID: 33027485 DOI: 10.1590/s0004-2803.202000000-64] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 06/26/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) appears to be common in patients with Crohn's disease (CD). The rate of SIBO has been estimated at 25%-88% in this setting. However, different demographic, socioeconomic, and disease-related factors may exist between South American and North American or European populations that may limit the generalization of these findings, as the data are mainly derived from North American or European studies. OBJECTIVE We studied the prevalence and predictors of SIBO in CD outpatients. METHODS In this retrospective study, between June 2011 and June 2016, the medical records of 110 CD patients were assessed for presence of SIBO using the H2/CH4 glucose breath test. Univariate analysis was performed to investigate the potential association between SIBO and demographic, disease-related data, systemic markers of inflammation (C-reactive protein and erythrocyte sedimentation rate). RESULTS The SIBO rate was high in CD patients (30%). Patients with and without SIBO were comparable according to demographics, systemic inflammatory biomarkers, and disease characteristics, except to the stricturing phenotype more common in the SIBO-positive CD patients (48.5% vs 19.5%, P=0.001). CONCLUSION In Brazilian CD patients, SIBO is a highly prevalent condition. Stricturing phenotype demonstrated association with SIBO. An individualized screening plan followed by the timely treatment for SIBO should be carried out as part of quality of care improvement in CD individuals.
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Costa RFA, Ferrari MLA, Bringer MA, Darfeuille-Michaud A, Martins FS, Barnich N. Characterization of mucosa-associated Escherichia coli strains isolated from Crohn's disease patients in Brazil. BMC Microbiol 2020; 20:178. [PMID: 32576138 PMCID: PMC7310525 DOI: 10.1186/s12866-020-01856-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background Crohn’s disease (CD) is characterized by chronic inflammation of the human intestine. Several studies have demonstrated that the intestinal mucosa of CD patients in Western countries is abnormally colonized by adherent-invasive Escherichia coli (AIEC) strains. However, no studies to date have focused on the involvement of such E. coli strains in CD patients in Brazil. Here, we characterized E. coli strains associated with the ileal mucosa of Brazilian CD patients (ileal biopsies from 35 subjects, 24 CD patients and 11 controls). Results The colonization level of adherent Enterobacteriaceae associated with the ileal mucosa of CD patients was significantly higher than that of the controls. The proportions of E. coli strains belonging to phylogroups B1 and B2 were two-fold higher in strains isolated from CD patients than in those isolated from controls. CD patients in the active phase harbored 10-fold more E. coli belonging to group B2 than CD patients in remission. Only a few E. coli isolates had invasive properties and the ability to survive within macrophages, but 25% of CD patients in Brazil (6/24) harbored at least one E. coli strain belonging to the AIEC pathobiont. However, fimH sequence analysis showed only a few polymorphisms in the FimH adhesin of strains isolated in this study compared to the FimH adhesin of AIEC collections isolated from European patients. Conclusions Mucosa-associated E. coli strains colonize the intestinal mucosa of Brazilian CD patients. However, the strains isolated from Brazilian CD patients have probably not yet co-evolved with their hosts and therefore have not fully developed a strong adherent-invasive phenotype. Thus, it will be crucial to follow in the future the emergence and evolution of AIEC pathobionts in the Brazilian population.
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Affiliation(s)
- Rafaella F A Costa
- Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.,Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRAE 2018, 28 place Henri Dunant, 63000, Clermont-Ferrand, France
| | - Maria L A Ferrari
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Marie-Agnès Bringer
- Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, F-21000, Dijon, France
| | - Arlette Darfeuille-Michaud
- Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRAE 2018, 28 place Henri Dunant, 63000, Clermont-Ferrand, France
| | - Flaviano S Martins
- Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Nicolas Barnich
- Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRAE 2018, 28 place Henri Dunant, 63000, Clermont-Ferrand, France.
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Strömbeck A, Lasson A, Strid H, Sundin J, Stotzer PO, Simrén M, Magnusson MK, Öhman L. Fecal microbiota composition is linked to the postoperative disease course in patients with Crohn's disease. BMC Gastroenterol 2020; 20:130. [PMID: 32366222 PMCID: PMC7197162 DOI: 10.1186/s12876-020-01281-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/22/2020] [Indexed: 12/17/2022] Open
Abstract
Background The role of the fecal microbiota composition for the postoperative disease course of patients with Crohn’s disease (CD) who have undergone ileocecal resection remains to be established. In this study, we investigated if the fecal microbiota composition, determined by a high throughput test quantifying a pre-selected set of bacteria, is associated with the postoperative disease course of CD patients. Methods Fecal samples were obtained from healthy subjects as well as from CD patients, 3–10 weeks and 1 year after ileocaecal resection. The fecal microbial composition was analyzed by Genetic Analysis GA-map Dysbiosis test, targeting ≥300 bacteria on different taxonomic levels. Postoperative disease status was assessed endoscopically according to Rutgeerts scoring system 1 year after surgery. Differences in fecal microbiota composition between groups were analyzed by multivariate factor analyses and cluster analysis. Microbial stability over time was determined using Bray-Curtis dissimilarity. Results One year after surgery, the fecal microbiota composition differed between CD patients (n = 21) and healthy subjects (n = 7). At this time point, the microbiota composition of CD patients was associated with disease course, clearly separating patients with disease relapse (n = 8) and patients in remission (n = 13). Further, the microbial within-patient stability was high during the first year after surgery, irrespective of disease course. Conclusion The fecal microbiota composition of CD patients, analyzed by GA-map Dysbiosis test, is subject to little variation over time, and may potentially be used as a non-invasive diagnostic tool for the postoperative disease course.
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Affiliation(s)
- Anna Strömbeck
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 435, 405 30, Gothenburg, Sweden.
| | - Anders Lasson
- Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden
| | - Hans Strid
- Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden
| | - Johanna Sundin
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 435, 405 30, Gothenburg, Sweden
| | - Per-Ove Stotzer
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Maria K Magnusson
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 435, 405 30, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 435, 405 30, Gothenburg, Sweden
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30
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Liu W, Zhou Y, Qin Y, Yu L, Li R, Chen Y, Xu Y. Effects of PM 2.5 exposure during gestation on maternal gut microbiota and pregnancy outcomes. CHEMOSPHERE 2020; 247:125879. [PMID: 31935575 DOI: 10.1016/j.chemosphere.2020.125879] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/06/2020] [Accepted: 01/08/2020] [Indexed: 06/10/2023]
Abstract
A number of studies have reported that fine particulate matter (PM2.5) exposure is associated with adverse pregnancy outcomes. Moreover, PM2.5 exposure contributes to changes of gut microbiota. However, influences of PM2.5 exposure during gestation on maternal gut microbiota and pregnancy outcomes were not well understood. Here we performed a study using mice models. Dams were exposed to PM2.5 suspension by intratracheal instillation on gestational day (GD) 3, 6, 9, 12 and 15. Pregnancy outcomes, maternal gut microbiota and short chain fatty acids on GD 18 were all measured. The fetal body weight of PM2.5 group was significantly lower than that of control group (p < 0.05). Meanwhile, the fetal body length of PM2.5 group was significantly shorter than that of control group (p < 0.05). The Shannon or Simpson index of PM2.5 group were higher than that of control group (p < 0.05). At the phyla level, compared to dams in control group, mice in the PM2.5 group had higher ratio of phyla Proteobacteria, Candidatus Saccharibacteria and Fusobacteria and lower ratio of phyla Acidobacteria, Gemmatimonadetes and Deferribacteres in the gut. Compared with control group, the concentration of isobutyric acid was higher in PM2.5 group, but butyric acid concentration was lower in PM2.5 group (p < 0.05). These findings suggested that prenatal exposure to PM2.5 had an effect on birth weight of fetus. Meanwhile, PM2.5 tracheal exposure during gestation caused changes in the distribution and structure of gut microbiota of dams.
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Affiliation(s)
- Wei Liu
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China
| | - Yalin Zhou
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China
| | - Yong Qin
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China
| | - Lanlan Yu
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China
| | - Ruijun Li
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China
| | - Yuhan Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China
| | - Yajun Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100083, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, Beijing, 100083, China.
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Machiels K, Pozuelo del Río M, Martinez-De la Torre A, Xie Z, Pascal Andreu V, Sabino J, Santiago A, Campos D, Wolthuis A, D’Hoore A, De Hertogh G, Ferrante M, Manichanh C, Vermeire S. Early Postoperative Endoscopic Recurrence in Crohn's Disease Is Characterised by Distinct Microbiota Recolonisation. J Crohns Colitis 2020; 14:1535-1546. [PMID: 32333762 PMCID: PMC7648170 DOI: 10.1093/ecco-jcc/jjaa081] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS Intestinal microbiota dysbiosis is implicated in Crohn's disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota. METHODS Mucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts score ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms. RESULTS The mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR] <0.01) and enrichment of Proteobacteria [FDR = 0.009] and Akkermansia spp. [FDR = 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDR <0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDR <0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDR = 0.003] and Actinomycineae [FDR = 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDR = 0.04] and Fusobacteria [FDR = 0.04] compared with patients without POR. CONCLUSIONS Microbiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.
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Affiliation(s)
- Kathleen Machiels
- Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | | | | | - Zixuan Xie
- Department of Gastroenterology, Vall d’Hebron Research Institute, Barcelona, Spain
| | | | - João Sabino
- Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Alba Santiago
- Department of Gastroenterology, Vall d’Hebron Research Institute, Barcelona, Spain
| | - David Campos
- Department of Gastroenterology, Vall d’Hebron Research Institute, Barcelona, Spain
| | - Albert Wolthuis
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - André D’Hoore
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Gert De Hertogh
- Department of Imaging & Pathology, KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Chaysavanh Manichanh
- Department of Gastroenterology, Vall d’Hebron Research Institute, Barcelona, Spain,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Séverine Vermeire
- Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium,Corresponding author: Severine Vermeire, MD, PhD, Department of Gastroenterology & Hepatology, University Hospitals Leuven, Herestraat 49 3000 Leuven, Belgium. Tel.: +32 16344225; fax +32 16344419;
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32
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Keita ÅV, Alkaissi LY, Holm EB, Heil SDS, Chassaing B, Darfeuille-Michaud A, McKay DM, Söderholm JD. Enhanced E. coli LF82 Translocation through the Follicle-associated Epithelium in Crohn's Disease is Dependent on Long Polar Fimbriae and CEACAM6 expression, and Increases Paracellular Permeability. J Crohns Colitis 2020; 14:216-229. [PMID: 31393983 PMCID: PMC7008151 DOI: 10.1093/ecco-jcc/jjz144] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Patients with Crohn's disease [CD] harbour an increased number of adherent-invasive E. coli [AIEC]. The strain LF82, identified in the ileal mucosa of CD patients, has been extensively studied for pathogenic mechanisms. However, understanding of the interaction of LF82 with the intestinal mucosa of CD patients is lacking. METHODS Here, we investigated the importance of long polar fimbriae [LPF] type 1 pili and the carcinoembryonic antigen-related cell-adhesion molecule 6 [CEACAM6] for translocation of LF82 in an in vitro model of follicle-associated epithelium [FAE], and in the FAE and villus epithelium [VE] of patients with CD and controls, using Ussing chambers. RESULTS Significantly greater LF82 passage occurred in the FAE model compared with in the VE Caco-2cl1 mono-culture. Moreover, bacterial translocation was inhibited by either LPF disruption or pre-incubation with anti-CEACAM6 antibody. Tissue mounted in Ussing chambers showed significantly higher LF82 passage in FAE from patients with CD compared with control FAE, that was diminished in LF82 lacking LPF and by blocking host CEACAM6. Interestingly, addition of LF82 to the CD FAE tissues significantly increased paracellular permeability [of 51Chromium-EDTA] compared with baseline, and the increase was inhibited by anti-CEACAM6. Immunofluorescence and immunoblots showed higher expression of CEACAM6 in FAE of patients with CD compared with in FAE from controls. CONCLUSIONS These data suggest that the FAE of CD patients is a site of vulnerability for invasion by LF82 via a mechanism that requires both bacterial LPF and host CEACAM6. Further, LF82 has the ability to increase paracellular passage through the FAE of patients with CD. These data can help define novel therapeutic targets in CD for the prevention of clinical recurrence.
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Affiliation(s)
- Åsa V Keita
- Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, Linköping, Sweden
| | - Lina Yakymenko Alkaissi
- Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, Linköping, Sweden
| | - Elin B Holm
- Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, Linköping, Sweden
| | - Stéphanie D S Heil
- Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, Linköping, Sweden
| | - Benoit Chassaing
- Neuroscience Institute and Institute for Biomedical Sciences, Georgia State University, Atlanta, USA
| | | | - Derek M McKay
- Gastrointestinal Research Group, Department of Physiology and Pharmacology, Snyder Institute for Chronic Disease, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Johan D Söderholm
- Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, Linköping, Sweden
- Department of Surgery, County Council of Östergötland, Linköping, Sweden
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Newman KM, Vaughn BP. Efficacy of intestinal microbiota transplantation in ulcerative colitis: a review of current literature and knowledge. MINERVA GASTROENTERO 2020; 65. [DOI: 10.23736/s1121-421x.19.02610-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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The role of major virulence factors and pathogenicity of adherent-invasive Escherichia coli in patients with Crohn's disease. GASTROENTEROLOGY REVIEW 2020; 15:279-288. [PMID: 33777266 PMCID: PMC7988836 DOI: 10.5114/pg.2020.93235] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel disease (IBD) is a term that describes Crohn's disease (CD) and ulcerative colitis (UC), and these two conditions are characterised by chronic inflammation of the gastrointestinal tract. Dysbiosis of intestinal microbiota has been consistently linked to patients with IBD. In the last two decades, the progressive implication of adherent-invasive Escherichia coli (AIEC) pathogenesis in patients with CD has been increasing. Here we discuss recent findings that indicate the role and mechanisms of AIEC in IBD. We also highlight AIEC virulence factor genes and mechanisms that suggest an important role in the severity of inflammation in CD patients. Finally, we emphasise data on the prevalence of AIEC in CD patients.
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35
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Chen L, Reynolds C, David R, Peace Brewer A. Development of an Index Score for Intestinal Inflammation-Associated Dysbiosis Using Real-World Stool Test Results. Dig Dis Sci 2020; 65:1111-1124. [PMID: 31529411 PMCID: PMC7069909 DOI: 10.1007/s10620-019-05828-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 09/04/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gut microbiota play an important role in human health. However, the application of gut microbiome in regular clinical practice is limited by interindividual variations and complexity of test results. HYPOTHESIS It is possible to address interindividual variation by using large data-based exploratory-pattern analysis. METHODS The current study was conducted using a large data set (n = 173,221) of nonselective incoming patients' test results from a stool test. The data set included assays for the detection of 24 selected commensal microorganisms and multiple biomarkers in feces. Patients were grouped based on their levels of inflammation biomarkers such as calprotectin, eosinophil protein X, and IgA. Group mean values of biomarkers and commensal microbes were used in an exploratory-pattern analysis for association from which an index score for intestinal inflammation-associated dysbiosis (IAD) was developed. The IAD score was evaluated in one questionnaire-based study (n = 7263) and one prospective case series study (n = 122) with patients of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease. RESULTS We identified a microbial profile strongly associated with fecal inflammation biomarkers. Developed on the pattern of the microbial profile, the IAD score demonstrated a strong association with fecal inflammation biomarkers and was significantly different between patients with IBD and those with IBS or celiac disease. CONCLUSION Using real-world data, we have developed a method to predict gut dysbiosis associated with different GI disease conditions. It may help clinicians simplify the process of interpreting gut microbial status and provide gut health assessment and treatment evaluation.
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Affiliation(s)
- Lihong Chen
- Department of Clinical Evidence Development, Genova Diagnostics, Inc, 63 Zillicoa Street, Asheville, NC 28801 USA
| | - Courtney Reynolds
- Department of Medicine, UCLA School of Medicine, Los Angeles, CA USA
| | - Robert David
- Department of Clinical Laboratory, Genova Diagnostics, Inc, 3425 Corporate Way, Duluth, GA 30096 USA
| | - Amy Peace Brewer
- Department of Clinical Laboratory, Genova Diagnostics, Inc, 63 Zillicoa Street, Asheville, NC 28801 USA
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Seishima J, Iida N, Kitamura K, Yutani M, Wang Z, Seki A, Yamashita T, Sakai Y, Honda M, Yamashita T, Kagaya T, Shirota Y, Fujinaga Y, Mizukoshi E, Kaneko S. Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host. Genome Biol 2019; 20:252. [PMID: 31767028 PMCID: PMC6876129 DOI: 10.1186/s13059-019-1879-9] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 11/04/2019] [Indexed: 12/14/2022] Open
Abstract
Background Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level. Results We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn’s disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10−/− mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients. Conclusions E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.
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Affiliation(s)
- Jun Seishima
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Noriho Iida
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Kazuya Kitamura
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Masahiro Yutani
- Department of Bacteriology, Graduate School of Medicinal Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Ziyu Wang
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Akihiro Seki
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Taro Yamashita
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Yoshio Sakai
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Masao Honda
- Department of Advanced Medical Technology, Graduate School of Health Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Tatsuya Yamashita
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Takashi Kagaya
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Yukihiro Shirota
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
| | - Yukako Fujinaga
- Department of Bacteriology, Graduate School of Medicinal Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Eishiro Mizukoshi
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan.
| | - Shuichi Kaneko
- Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan
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Ulrich RJ, Bott J, Imlay H, Lopez K, Cinti S, Rao K. Clostridioides difficile Enteritis in Patients Following Total Colectomy-a Rare but Genuine Clinical Entity. Open Forum Infect Dis 2019; 6:ofz409. [PMID: 31687419 PMCID: PMC6822686 DOI: 10.1093/ofid/ofz409] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 09/10/2019] [Indexed: 02/07/2023] Open
Abstract
Objective Clostridioides difficile infection (CDI) frequently causes colitis following antibiotic exposure and is a leading cause of gastrointestinal infectious mortality. Infection in the small bowel, C. difficile enteritis (CDE), was previously thought impossible, but case series have challenged this dogma. Clostridioides difficile enteritis prevalence, severity, and potential risk factors are unknown. Methods We retrospectively analyzed all total colectomy patients over a 20-year period at our institution. C. difficile enteritis was defined by clinical symptoms and positive C. difficile stool testing after colectomy. We compared CDE cases to controls using multivariable analysis to identify potential CDE risk factors. Results C. difficile enteritis occurred in 44 of 855 (5.1%) patients, a median of 130 days after colectomy. Compared to controls, CDE patients were similar in age, gender, and presence of immunosuppression. The majority (64%) had antibiotics <30 days prior to CDE. In multivariable analysis, CDE risk factors included perioperative acid suppression (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.26–5.04; P = .009), colectomy for inflammatory bowel disease (HR, 2.95; CI, 1.29–6.72; P = .010), colectomy for CDI (HR, 9.95; CI, 2.70–36.63; P ≤ .001), and β-lactam use in the setting of enteral feeds (HR, 17.83; CI, 2.75–115.68; P = .003). C. difficile enteritis presented with severe disease half of the time, with 81.8% requiring hospitalization. Conclusions C. difficile enteritis is a rare clinical entity that should be considered in postcolectomy patients presenting with CDI symptoms, even years after surgery. Like traditional CDI, likely CDE risk factors include acid suppression and inflammatory bowel disease. Prior antibiotic use in the setting of enteral feeds may amplify CDE risk. C. difficile enteritis often presents as severe disease and frequently requires hospitalization.
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Affiliation(s)
- Robert J Ulrich
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Jonathan Bott
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.,Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Hannah Imlay
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Kerri Lopez
- University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Sandro Cinti
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.,Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Krishna Rao
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.,Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA.,Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
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Abstract
The present review is focused on the prebiotic impact of inulin on the management of the gastrointestinal disorder. Prebiotics can be described as "non-digestible food ingredient stimulating the growth of a certain number of bacteria in the colon, which can improve the host health". In 2004 this definition was modernized to include other areas that may benefit from selective targeting of particular microorganisms: "selectively fermented ingredients that alter the configuration and activity in the gastrointestinal microbiota that confer positive effect". The positive impact of prebiotics in experimental colitis and human inflammatory bowel disease (IBD) has already been established. Prebiotics shows a positive effect in the prevention of IBD by modulating the trophic functions of the flora. Inulin enhances the growth of indigenous lactobacilli and/or bifidobacteria by inducing colonic production of short chain fatty acids (SCFA's) and these properties are related to decreased mucosal lesion scores and diminished mucosal inflammation. Inulin shows a positive approach to retain microbial populations and to support epithelial barrier function by their prebiotic effect which helps in the host defense against invasion and pathogens translocation (endogenous and/or exogenous) and in the inhibition of gastrointestinal diseases and this impact should be verified in further clinical studies. In the present review, we discussed the positive effect of prebiotics in rat IBD models and in human subjects along with their potential protective mechanisms. Preclinical and clinical data revealed that the gut mucosal barrier would be improved by the use of prebiotics in IBD.
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Affiliation(s)
- Wasim Akram
- School of Studies in Pharmaceutical Sciences, Jiwaji University
| | - Navneet Garud
- School of Studies in Pharmaceutical Sciences, Jiwaji University
| | - Ramakant Joshi
- School of Studies in Pharmaceutical Sciences, Jiwaji University
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39
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Muñiz Pedrogo DA, Chen J, Hillmann B, Jeraldo P, Al-Ghalith G, Taneja V, Davis JM, Knights D, Nelson H, Faubion WA, Raffals L, Kashyap PC. An Increased Abundance of Clostridiaceae Characterizes Arthritis in Inflammatory Bowel Disease and Rheumatoid Arthritis: A Cross-sectional Study. Inflamm Bowel Dis 2019; 25:902-913. [PMID: 30321331 PMCID: PMC6458525 DOI: 10.1093/ibd/izy318] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) are a group of heterogeneous inflammatory conditions affecting the gastrointestinal tract. Although there is considerable evidence linking the gut microbiota to intestinal inflammation, there is limited knowledge on its potential role in the development of extraintestinal manifestations of IBD. METHODS Four groups of patients were included: IBD-associated arthropathy (IBD-A); IBD without arthropathy (IBD-N); rheumatoid arthritis (RA); and non-IBD, nonarthritis controls. DNA from stool samples was isolated and sequenced using the Illumina platform. Paired-end reads were quality-controlled using SHI7 and processed with SHOGUN. Abundance and diversity analyses were performed using QIIME, and compositional biomarker identification was performed using LEfSe. RESULTS One hundred eighty patients were included in the analysis. IBD-A was associated with an increased abundance of microbial tyrosine degradation pathways when compared with IBD-N (P = 0.02), whereas IBD-A and RA patients both shared an increased abundance of Clostridiaceae when compared with controls (P = 0.045). We found that history of bowel surgery was a significant source of variability (P = 0.001) among all IBD patients and was associated with decreased alpha diversity and increased abundance of Enterobacteriaceae (P = 0.004). CONCLUSIONS An increased abundance of gut microbial tyrosine degradation pathways was associated with IBD-A. An increased abundance of Clostridiaceae was shared by both IBD-A and RA patients and suggests a potentially common microbial link for inflammatory arthritis. The increased abundance of Enterobacteriaceae, previously reported in IBD, may be due to the effects of previous bowel surgery and highlights the importance of controlling for this variable in future studies.
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Affiliation(s)
- David A Muñiz Pedrogo
- Center for Clinical and Translational Science, Mayo Clinic, Rochester, Minnesota,University of Puerto Rico School of Medicine, San Juan, Puerto Rico
| | - Jun Chen
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
| | - Benjamin Hillmann
- Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota
| | | | - Gabriel Al-Ghalith
- Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota
| | - Veena Taneja
- Department of Immunology, Mayo Clinic, Rochester, Minnesota
| | - John M Davis
- Division of Rheumatology, Mayo Clinic, Rochester, Minnesota
| | - Dan Knights
- Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota
| | - Heidi Nelson
- Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Laura Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Purna C Kashyap
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,Address correspondence to: Purna C. Kashyap, MBBS, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905 ()
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40
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Gong J, Chehrazi-Raffle A, Placencio-Hickok V, Guan M, Hendifar A, Salgia R. The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies. Clin Transl Med 2019; 8:9. [PMID: 30887236 PMCID: PMC6423251 DOI: 10.1186/s40169-019-0225-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 03/08/2019] [Indexed: 02/06/2023] Open
Abstract
There is growing interest in identifying predictive biomarkers for inhibitors of programmed cell death protein 1 receptor (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). Given the links between the stool microbiota, anticancer immunosurveillance, and general health, the composition of the gut microbiome has recently undergone investigation as a biomarker for immunotherapy. In this review, we highlight published results from preclinical and clinical studies to date supporting a relationship between the gut microbiome and antitumor efficacy of immune checkpoint inhibitors. Despite the promising and hypothesis-generating findings that have been produced in this arena to date, there remain some inconsistencies amongst present data that may need to be resolved to contribute to further development. Among these, a better understanding of the immunomodulatory function of the microbiome, standardization in sampling, sequencing techniques, and data analysis, and ensuring uniformity across various aspects of study design are warranted in conducting future prospective studies seeking to validate the gut microbiome as a potential biomarker of response to checkpoint blockade.
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Affiliation(s)
- Jun Gong
- Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 USA
| | - Alexander Chehrazi-Raffle
- Department of Internal Medicine, Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509 USA
| | - Veronica Placencio-Hickok
- Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 USA
| | - Michelle Guan
- Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 USA
| | - Andrew Hendifar
- Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 USA
| | - Ravi Salgia
- Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Building 51, Room 101, 1500 E Duarte St, Duarte, CA 91010 USA
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41
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M'Koma AE. The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview. GASTROINTESTINAL DISORDERS 2019; 1:75-105. [PMID: 37577036 PMCID: PMC10416806 DOI: 10.3390/gidisord1010007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between genetic risk factors, the intestinal microbiota, urbanization, modernization, Westernization, the environmental influences and immune responses in the etiopathogenesis of inflammatory bowel disease in humans. Inflammatory bowel disease is an expensive multifactorial debilitating disease that affects thousands new people annually worldwide with no known etiology or cure. The conservative therapeutics focus on the established pathology where the immune dysfunction and gut injury have already happened but do not preclude or delay the progression. Inflammatory bowel disease is evolving globally and has become a global emergence disease. It is largely known to be a disease in industrial-urbanized societies attributed to modernization and Westernized lifestyle associated with environmental factors to genetically susceptible individuals with determined failure to process certain commensal antigens. In the developing nations, increasing incidence and prevalence of inflammatory bowel disease (IBD) has been associated with rapid urbanization, modernization and Westernization of the population. In summary, there are identified multiple associations to host exposures potentiating the landscape risk hazards of inflammatory bowel disease trigger, that include: Western life-style and diet, host genetics, altered innate and/or acquired/adaptive host immune responses, early-life microbiota exposure, change in microbiome symbiotic relationship (dysbiosis/dysbacteriosis), pollution, changing hygiene status, socioeconomic status and several other environmental factors have long-standing effects/influence tolerance. The ongoing multipronged robotic studies on gut microbiota composition disparate patterns between the rural vs. urban locations may help elucidate and better understand the contribution of microbiome disciplines/ecology and evolutionary biology in potentially protecting against the development of inflammatory bowel disease.
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Affiliation(s)
- Amosy E M'Koma
- Meharry Medical College School of Medicine, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Nashville, TN 37208, USA
- Vanderbilt University School of Medicine, Department of Surgery, Colon and Rectal Surgery, Nashville, TN 37232, USA
- The American Society of Colon and Rectal Surgeons (ASCRS), Arlington Heights, IL 60005, USA
- The American Gastroenterological Association (AGA), Bethesda, MD 20814, USA
- Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, USA
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42
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Schoultz I, Keita ÅV. Cellular and Molecular Therapeutic Targets in Inflammatory Bowel Disease-Focusing on Intestinal Barrier Function. Cells 2019; 8:193. [PMID: 30813280 PMCID: PMC6407030 DOI: 10.3390/cells8020193] [Citation(s) in RCA: 130] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 02/18/2019] [Accepted: 02/21/2019] [Indexed: 02/06/2023] Open
Abstract
The human gut relies on several cellular and molecular mechanisms to allow for an intact and dynamical intestinal barrier. Normally, only small amounts of luminal content pass the mucosa, however, if the control is broken it can lead to enhanced passage, which might damage the mucosa, leading to pathological conditions, such as inflammatory bowel disease (IBD). It is well established that genetic, environmental, and immunological factors all contribute in the pathogenesis of IBD, and a disturbed intestinal barrier function has become a hallmark of the disease. Genetical studies support the involvement of intestinal barrier as several susceptibility genes for IBD encode proteins with key functions in gut barrier and homeostasis. IBD patients are associated with loss in bacterial diversity and shifts in the microbiota, with a possible link to local inflammation. Furthermore, alterations of immune cells and several neuro-immune signaling pathways in the lamina propria have been demonstrated. An inappropriate immune activation might lead to mucosal inflammation, with elevated secretion of pro-inflammatory cytokines that can affect the epithelium and promote a leakier barrier. This review will focus on the main cells and molecular mechanisms in IBD and how these can be targeted in order to improve intestinal barrier function and reduce inflammation.
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Affiliation(s)
- Ida Schoultz
- School of Medical Sciences, Örebro University, 703 62 Örebro, Sweden.
| | - Åsa V Keita
- Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, 581 85 Linköping, Sweden.
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43
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Role of Dietary Lipids in Modulating Inflammation through the Gut Microbiota. Nutrients 2019; 11:nu11010117. [PMID: 30626117 PMCID: PMC6357048 DOI: 10.3390/nu11010117] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 12/19/2018] [Accepted: 12/30/2018] [Indexed: 12/12/2022] Open
Abstract
Inflammation and its resolution is a tenuous balance that is under constant contest. Though several regulatory mechanisms are employed to maintain homeostasis, disruptions in the regulation of inflammation can lead to detrimental effects for the host. Of note, the gut and microbial dysbiosis are implicated in the pathology of systemic chronic low-grade inflammation which has been linked to several metabolic diseases. What remains to be described is the extent to which dietary fat and concomitant changes in the gut microbiota contribute to, or arise from, the onset of metabolic disorders. The present review will highlight the role of microorganisms in host energy regulation and several mechanisms that contribute to inflammatory pathways. This review will also discuss the immunomodulatory effects of the endocannabinoid system and its link with the gut microbiota. Finally, a brief discussion arguing for improved taxonomic resolution (at the species and strain level) is needed to deepen our current knowledge of the microbiota and host inflammatory state.
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44
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Abstract
Despite the revolution in inflammatory bowel disease (IBD) treatment over the past two decades with the advent of biological therapies, there remains a substantial proportion of patients with inadequate or unsustained response to existent therapies. The overwhelming focus of IBD therapeutics has been targeting mucosal immunity, however with the developing evidence base pointing to the role of gut microbes in the inflammatory process, renewed focus should be placed on the impact of manipulating the microbiome in IBD management. This review provides an overview of the evidence implicating bacteria in the pathogenesis of gut inflammation in IBD and provides an overview of the evidence of antibiotics in IBD treatment. We also suggest a potential role of antibiotics in clinical practice based on available evidence and clinical experience.
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Affiliation(s)
- Oren Ledder
- Shaare Zedek Medical Center, Jerusalem, Israel.,The Hebrew University of Jerusalem, Jerusalem, Israel
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45
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Bretin A, Lucas C, Larabi A, Dalmasso G, Billard E, Barnich N, Bonnet R, Nguyen HTT. AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation. Sci Rep 2018; 8:12301. [PMID: 30120269 PMCID: PMC6098085 DOI: 10.1038/s41598-018-30055-y] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 07/21/2018] [Indexed: 12/12/2022] Open
Abstract
A high prevalence of adherent-invasive E. coli (AIEC) in the intestinal mucosa of Crohn's disease patients has been shown. AIEC colonize the intestine and induce inflammation in genetically predisposed mouse models including CEABAC10 transgenic (Tg) mice expressing human CEACAM6-receptor for AIEC and eif2ak4-/- mice exhibiting autophagy defect in response to AIEC infection. Here, we aimed at investigating whether gut microbiota modification contributes to AIEC-induced intestinal inflammation in these mouse models. For this, eif2ak4+/+ and eif2ak4-/- mice or CEABAC10 Tg mice invalidated for Eif2ak4 gene (Tg/eif2ak4-/-) or not (Tg/eif2ak4+/+) were infected with the AIEC reference strain LF82 or the non-pathogenic E. coli K12 MG1655 strain. In all mouse groups, LF82 colonized the gut better and longer than MG1655. No difference in fecal microbiota composition was observed in eif2ak4+/+ and eif2ak4-/- mice before infection and at day 1 and 4 post-infection. LF82-infected eif2ak4-/- mice exhibited altered fecal microbiota composition at day 14 and 21 post-infection and increased fecal lipocalin-2 level at day 21 post-infection compared to other groups, indicating that intestinal inflammation developed after microbiota modification. Similar results were obtained for LF82-infected Tg/eif2ak4-/- mice. These results suggest that in genetically predisposed hosts, AIEC colonization might induce chronic intestinal inflammation by altering the gut microbiota composition.
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Affiliation(s)
- Alexis Bretin
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
| | - Cécily Lucas
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
| | - Anaïs Larabi
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
| | - Guillaume Dalmasso
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
| | - Elisabeth Billard
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
| | - Nicolas Barnich
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
| | - Richard Bonnet
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France
- Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, 63001, France
| | - Hang Thi Thu Nguyen
- M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
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46
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Ledder O, Turner D. Antibiotics in IBD: Still a Role in the Biological Era? Inflamm Bowel Dis 2018; 24:1676-1688. [PMID: 29722812 DOI: 10.1093/ibd/izy067] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Indexed: 02/06/2023]
Abstract
Despite compelling evidence pointing to a critical role of gut microflora in inflammatory bowel disease (IBD) pathogenesis, the role of antibiotics in clinical practice remains limited, largely due to heterogeneous trials with often conflicting evidence. In this review, we revisit previous randomized controlled trials and high-quality uncontrolled studies in an effort to better elucidate the role of antibiotics in contemporary treatment algorithms. The most established role of antibiotics is in perianal Crohn's disease (CD), utilizing ciprofloxacin with or without metronidazole often as an adjunct to biological therapy. Evidence also points to a likely modest role of various antibiotic classes in mild to moderate luminal CD, including ciprofloxacin, metronidazole, azithromycin, and rifaximin. The benefit of metronidazole in preventing postoperative recurrence in CD is well reported; however, the long-term benefit of this intervention remains uncertain. The use of antibiotics in ulcerative colitis (UC) is even more controversial, but studies using broad-spectrum oral antibiotic cocktails have reported a possible role in acute severe colitis and chronic persistent UC. Similarly, the role of oral vancomycin and gentamicin in very early-onset IBD has interesting preliminary results. Adverse events of antibiotics, the resulting alterations in the microbiome with its associated unknown long-term sequela, and the emergence of antibiotic-resistant strains must be carefully balanced. Therefore, although antibiotics may be underused in the treatment of IBD, their integration into clinical practice must be approached judiciously and individually.
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Affiliation(s)
- Oren Ledder
- Shaare Zedek Medical Center, Jerusalem, Israel.,The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Dan Turner
- Shaare Zedek Medical Center, Jerusalem, Israel.,The Hebrew University of Jerusalem, Jerusalem, Israel
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47
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Skowron KB, Shogan BD, Rubin DT, Hyman NH. The New Frontier: the Intestinal Microbiome and Surgery. J Gastrointest Surg 2018; 22:1277-1285. [PMID: 29633119 DOI: 10.1007/s11605-018-3744-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 03/12/2018] [Indexed: 01/31/2023]
Abstract
The microbiome exerts a remarkable effect on human physiology. The study of the human-microbiome relationship is a burgeoning field with great potential to improve our understanding of health and disease. In this review, we address common surgical problems influenced by the human microbiome and explore what is thus far known about this relationship. These include inflammatory bowel disease, colorectal neoplasms, and diverticular disease. We will also discuss the effect of the microbiome on surgical complications, specifically anastomotic leak. We hope that further research in this field will enlighten our management of these and other surgical problems.
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Affiliation(s)
- Kinga B Skowron
- Department of Surgery, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 5095, Chicago, IL, 60637, USA
| | - Benjamin D Shogan
- Department of Surgery, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 5095, Chicago, IL, 60637, USA.
| | - David T Rubin
- Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Neil H Hyman
- Department of Surgery, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 5095, Chicago, IL, 60637, USA
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48
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Hamilton AL, Kamm MA, Ng SC, Morrison M. Proteus spp. as Putative Gastrointestinal Pathogens. Clin Microbiol Rev 2018; 31:e00085-17. [PMID: 29899011 PMCID: PMC6056842 DOI: 10.1128/cmr.00085-17] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Proteus species, members of the Enterobacteriaceae family, are usually considered commensals in the gut and are most commonly recognized clinically as a cause of urinary tract infections. However, the recent identification of Proteus spp. as potential pathogens in Crohn's disease recurrence after intestinal resection serves as a stimulus to examine their potential role as gut pathogens. Proteus species possess many virulence factors potentially relevant to gastrointestinal pathogenicity, including motility; adherence; the production of urease, hemolysins, and IgA proteases; and the ability to acquire antibiotic resistance. Gastrointestinal conditions that have been linked to Proteus include gastroenteritis (spontaneous and foodborne), nosocomial infections, appendicitis, colonization of devices such as nasogastric tubes, and Crohn's disease. The association of Proteus species with Crohn's disease was particularly strong. Proteus species are low-abundance commensals of the human gut that harbor significant pathogenic potential; further investigation is needed.
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Affiliation(s)
- Amy L Hamilton
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Mark Morrison
- The University of Queensland Diamantina Institute, Faculty of Medicine, Translational Research Institute, Brisbane, Australia
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49
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Endospore forming bacteria may be associated with maintenance of surgically-induced remission in Crohn's disease. Sci Rep 2018; 8:9734. [PMID: 29950676 PMCID: PMC6021420 DOI: 10.1038/s41598-018-28071-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 06/14/2018] [Indexed: 12/28/2022] Open
Abstract
Crohn’s disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.
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Abstract
Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.
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Affiliation(s)
- Audrey Humphries
- a Department of Medicine , Division of Hematology/Oncology, University of California San Francisco , San Francisco , CA , USA
| | - Adil Daud
- a Department of Medicine , Division of Hematology/Oncology, University of California San Francisco , San Francisco , CA , USA
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