The Gut Microbiome and Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host–microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Metagenomic alterations in gut microbiota precede and predict onset of colitis in the IL10 gene-deficient murine model

10.1101/2020.05.04.078022 ◽

2020 ◽

Author(s):

Jun Miyoshi ◽

Sonny T. M. Lee ◽

Megan Kennedy ◽

Mora Puertolas ◽

Mary Frith ◽

...

Keyword(s):

Gut Microbiota ◽

Clinical Outcomes ◽

Murine Model ◽

Inflammatory Bowel Diseases ◽

Gut Microbiome ◽

Predictive Biomarkers ◽

Disease Outcomes ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Robust Measures

AbstractBackground & AimsInflammatory bowel diseases (IBD) are chronic inflammatory disorders where predictive biomarkers for the disease development and clinical course are sorely needed for development of prevention and early intervention strategies that can be implemented to improve clinical outcomes. Since gut microbiome alterations can reflect and/or contribute to impending host health changes, we examined whether gut microbiota metagenomic profiles would provide more robust measures for predicting disease outcomes in colitis-prone hosts.MethodsUsing the IL-10 gene-deficient (IL-10 KO) murine model where early life dysbiosis from antibiotic (cefoperozone, CPZ) treated dams vertically-transferred to pups increases risk for colitis later in life, we investigated temporal metagenomic profiles in the gut microbiota of post-weaning offspring and determined their relationship to eventual clinical outcomes.ResultsCompared to controls, offspring acquiring maternal CPZ-induced dysbiosis exhibited a restructuring of intestinal microbial membership both in bacteriome and mycobiome that were associated with alterations in specific functional subsystems. Furthermore, among IL-10 KO offspring from CPZ-treated dams, several functional subsystems, particularly nitrogen metabolism, diverged between mice that developed spontaneous colitis (CPZ-colitis) versus those that did not (CPZ-no-colitis) at a time point prior to eventual clinical outcome.ConclusionsOur findings provide support that functional metagenomic profiling of gut microbes has potential and promise meriting further study for development of tools to assess risk and manage human IBD.SynopsisCurrently, predictive markers for the development and course of inflammatory bowel diseases (IBD) are not available. This study supports the notion that gut microbiome metagenomic profiles could be developed into a useful tool to assess risk and manage human IBD.

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The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation

Cells ◽

10.3390/cells9051234 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1234 ◽

Cited By ~ 4

Author(s):

Chiara Amoroso ◽

Federica Perillo ◽

Francesco Strati ◽

Massimo Fantini ◽

Flavio Caprioli ◽

...

Keyword(s):

Gut Microbiota ◽

Immune Responses ◽

Targeted Therapies ◽

Intestinal Inflammation ◽

Cost Effective ◽

Bowel Diseases ◽

Current Therapies ◽

Microbe Interactions ◽

Inflammatory Bowel ◽

Host Microbe Interactions

Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host−microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.

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Host–microbe interactions in the gut: lessons learned from models of inflammatory bowel diseases

LymphoSign Journal ◽

10.14785/lpsn-2014-0014 ◽

2014 ◽

Vol 1 (2) ◽

pp. 61-76

Author(s):

Eytan Wine

Keyword(s):

Immune System ◽

Animal Models ◽

Patient Care ◽

Inflammatory Bowel Diseases ◽

Gut Microbes ◽

Bowel Diseases ◽

Microbe Interactions ◽

Inflammatory Bowel ◽

Host Microbe Interactions

The mammalian gut is the richest immune organ in the body and serves as a central location for immune system development, processing, and education. Inflammatory bowel diseases (IBD) provide excellent models for studying both innate and adaptive responses to gut microbes and the host-immune system – microbe interactions in the gut. Microbes are linked to almost all of the known disease-associated genetic polymorphisms in IBD and are critical mediators of environmental effects (through food, hygiene, and infection). Human and animal-based research supports the central role of microbes in IBD pathogenesis at multiple levels. Animal models of IBD only develop in the presence of microbes, and co-housing mice that are genetically susceptible to gut inflammation with normal mice can lead to the development of bowel injury. Recent advances in research technologies, such as deep-sequencing that enables detailed compositional analyses, have revolutionized the study of host–microbe interactions in the gut; however, knowing which bacteria are present in the bowel is likely not sufficient. The function of the microbiota as a community is recognized as a critical factor for gut homeostasis. Animal models of IBD have provided critical insight into basic biology and disease pathogenesis, especially regarding the role of microbes in IBD pathogenesis. Although many of these recent discoveries on host–microbe interactions are not yet applied to patient care, these basic observations will certainly revolutionize patient care in the future. Using such data, we may be able to predict risk of disease, define biological subtypes, establish tools for prevention, and even cure IBD using microbes or their products. A broad spectrum of therapeutic tools spanning from fecal transplantation, probiotics, prebiotics, and microbial products to microbe-tailored diets may supplement current IBD treatments.

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Gut microbiota induce local and systemic CD4 T cell responses in healthy individuals that are altered in inflammatory bowel diseases

10.1055/s-0037-1604874 ◽

2017 ◽

Author(s):

AN Hegazy ◽

N West ◽

MJT Stubbington ◽

E Wendt ◽

K Suijker ◽

...

Keyword(s):

T Cell ◽

Gut Microbiota ◽

Inflammatory Bowel Diseases ◽

T Cell Responses ◽

Cd4 T Cell ◽

Healthy Individuals ◽

Cell Responses ◽

Bowel Diseases ◽

Inflammatory Bowel

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Gut microbiota in inflammatory bowel diseases: moving from basic science to clinical applications

Human Genetics ◽

10.1007/s00439-020-02218-3 ◽

2020 ◽

Author(s):

Valerie Collij ◽

Marjolein A. Y. Klaassen ◽

Rinse K. Weersma ◽

Arnau Vich Vila

Keyword(s):

Gut Microbiota ◽

Inflammatory Bowel Diseases ◽

Basic Science ◽

Clinical Applications ◽

Bowel Diseases ◽

Inflammatory Bowel

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The Use of Probiotic Therapy to Modulate the Gut Microbiota and Dendritic Cell Responses in Inflammatory Bowel Diseases

Medical Sciences ◽

10.3390/medsci7020033 ◽

2019 ◽

Vol 7 (2) ◽

pp. 33 ◽

Cited By ~ 2

Author(s):

Pablo Alagón Fernández del Campo ◽

Alejandro De Orta Pando ◽

Juan Ignacio Straface ◽

José Ricardo López Vega ◽

Diego Toledo Plata ◽

...

Keyword(s):

Gut Microbiota ◽

Inflammatory Bowel Diseases ◽

T Regulatory Cells ◽

Oxygen Species ◽

Regulatory Cells ◽

Population Status ◽

Cell Responses ◽

Bowel Diseases ◽

Tolerance Response ◽

Inflammatory Bowel

: Recent investigations have shown that different conditions such as diet, the overuse of antibiotics or the colonization of pathogenic microorganisms can alter the population status of the intestinal microbiota. This modification can produce a change from homeostasis to a condition known as imbalance or dysbiosis; however, the role-played by dysbiosis and the development of inflammatory bowel diseases (IBD) has been poorly understood. It was actually not until a few years ago that studies started to develop regarding the role that dendritic cells (DC) of intestinal mucosa play in the sensing of the gut microbiota population. The latest studies have focused on describing the DC modulation, specifically on tolerance response involving T regulatory cells or on the inflammatory response involving reactive oxygen species and tissue damage. Furthermore, the latest studies have also focused on the protective and restorative effect of the population of the gut microbiota given by probiotic therapy, targeting IBD and other intestinal pathologies. In the present work, the authors propose and summarize a recently studied complex axis of interaction between the population of the gut microbiota, the sensing of the DC and its modulation towards tolerance and inflammation, the development of IBD and the protective and restorative effect of probiotics on other intestinal pathologies.

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