Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic relapsing–remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.

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Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease

Nutrients ◽

10.3390/nu14010004 ◽

2021 ◽

Vol 14 (1) ◽

pp. 4

Author(s):

Lara Hart ◽

Charlotte M. Verburgt ◽

Eytan Wine ◽

Mary Zachos ◽

Alisha Poppen ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gut Microbiome ◽

Low Cost ◽

Autoimmune Disorder ◽

Nutritional Therapy ◽

Intestinal Microbiome ◽

Microbial Composition ◽

Inflammatory Bowel ◽

And Function

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician.

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Gastrointestinal Inflammation and the Gut Microbiome: An Evolving Conceptual Framework with Implications for Diagnosis and Therapy in Inflammatory Bowel Disorders

EMJ Microbiology & Infectious Diseases ◽

10.33590/emjmicrobiolinfectdis/20-00050 ◽

2020 ◽

pp. 42-50

Author(s):

Oliver Grundmann

Keyword(s):

Inflammatory Bowel Disease ◽

Systemic Inflammation ◽

Bowel Disease ◽

Gut Microbiome ◽

Pathogenic Bacteria ◽

Bacterial Species ◽

Commensal Bacteria ◽

Low Grade ◽

Environmental Toxicants ◽

Inflammatory Bowel

The human gut microbiome has garnered much attention over the past two decades with important discoveries linking it to human health and disease. The commensal bacterial flora evolves due to the influence of a number of factors including diet, pathogen exposure, environmental toxicants, disease states, and a challenged microenvironment that requires balancing with the host itself. However, the composition of bacterial species can impact and contribute to the development of local and systemic inflammation. Among the factors attributed to intestinal inflammation are dysbiosis caused by pathogenic bacteria, following decreased host immunity or loss of intestinal barrier function. Dysbiosis can also be triggered by antibiotic therapy or the use of other medications that allow for colonisation of pathogenic bacteria, such as proton pump inhibitors. The imbalance with commensal bacteria leads to the generation of proinflammatory mediators and a reduction of host immune defences, due to a lack of short-chain fatty acid generation needed for energy production to maintain barrier and immune function. The initially localised inflammation results in further dysbiosis as former commensal bacteria are able to breach the barrier and cause systemic immune responses. Low-grade systemic inflammation is a hallmark of inflammatory bowel disease. Because a specific dysbiosis is common in patients with inflammatory bowel disease, it can serve as an early diagnostic marker in its development. Furthermore, faecal microbiome transplants have shown promising benefits in patients with ulcerative colitis and Crohn’s disease.

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The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of Inflammatory Bowel Disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00163.2021 ◽

2021 ◽

Author(s):

Joerg Ermann ◽

Mederbek Matmusaev ◽

Emma Haley ◽

Clemens Braun ◽

Felix Jost ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Model ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Intestinal Microbiome ◽

Intestinal Immune System ◽

Pharmacokinetic Properties ◽

Inflammatory Bowel ◽

The Impact ◽

Human And Mouse

ABSTRACT Background and Aims : Mouse and human data implicates the NOD1 and NOD2 sensors of the intestinal microbiome and the associated signal transduction via the RIPK2 kinase as a potentially key signaling node for the development of Inflammatory Bowel Disease (IBD) and an attractive target for pharmacologic intervention. The TRUC mouse model of IBD has been strongly indicated for evaluating the impact of RIPK2 antagonism on intestinal inflammation based on previous studies with NOD1, NOD2 and RIPK2 knockout mice. Methods. We identified and profiled the BI 706039 molecule as a potent and specific functional inhibitor of both human and mouse RIPK2 and with favorable pharmacokinetic properties. We dosed BI 706039 in the spontaneous TRUC mouse model from aged day 28 through aged day 56. Results : Oral, daily administration of BI 706039 caused dose-responsive and significant improvement in colonic histopathological inflammation, colon weight and terminal levels of protein normalized fecal lipocalin (all p< 0.001). These observations correlated with dose-responsively increasing systemic levels of the BI 706039 compound, splenic molecular target engagement of RIPK2 and modulation of inflammatory genes in the colon. Conclusions : A relatively low oral dose of a potent and selective RIPK2 inhibitor can block the signaling interface between the intestinal microbiome and the intestinal immune system and significantly improve disease associated intestinal inflammation.

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Microbial Sensing by the Intestinal Epithelium in the Pathogenesis of Inflammatory Bowel Disease

International Journal of Inflammation ◽

10.4061/2010/671258 ◽

2010 ◽

Vol 2010 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Michael Scharl ◽

Gerhard Rogler

Keyword(s):

Inflammatory Bowel Disease ◽

Immune System ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Innate Immune System ◽

Pathogenic Bacteria ◽

Intestinal Inflammation ◽

Innate Immune ◽

Model Systems ◽

Inflammatory Bowel

Recent years have raised evidence that the intestinal microbiota plays a crucial role in the pathogenesis of chronic inflammatory bowels diseases. This evidence comes from several observations. First, animals raised under germ-free conditions do not develop intestinal inflammation in several different model systems. Second, antibiotics are able to modulate the course of experimental colitis. Third, genetic polymorphisms in a variety of genes of the innate immune system have been associated with chronic intestinal inflammatory diseases. Dysfunction of these molecules results in an inappropriate response to bacterial and antigenic stimulation of the innate immune system in the gastrointestinal tract. Variants of pattern recognition receptors such as NOD2 or TLRs by which commensal and pathogenic bacteria can be detected have been shown to be involved in the pathogenesis of IBD. But not only pathways of microbial detection but also intracellular ways of bacterial processing such as autophagosome function are associated with the risk to develop Crohn's disease. Thus, the “environment concept” and the “genetic concept” of inflammatory bowel disease pathophysiology are converging via the intestinal microbiota and the recognition mechanisms for an invasion of members of the microbiota into the mucosa.

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Dietary Supplementation with Vitamin D, Fish Oil or Resveratrol Modulates the Gut Microbiome in Inflammatory Bowel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms23010206 ◽

2021 ◽

Vol 23 (1) ◽

pp. 206

Author(s):

Vivian Naa Amua Wellington ◽

Vijaya Lakshmi Sundaram ◽

Soudamani Singh ◽

Uma Sundaram

Keyword(s):

Inflammatory Bowel Disease ◽

Vitamin D ◽

Fish Oil ◽

Dietary Supplements ◽

Bowel Disease ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Human Microbiome ◽

Dietary Supplementation ◽

Inflammatory Bowel

Gastrointestinal health is influenced by the functional genes and metabolites generated by the human microbiome. As the volume of current biomedical and translational research indicates, the importance and impact of this ecosystem of microorganisms, especially those comprising the gut microbiome on human health, has become increasingly apparent. Changes to the gut microbiome are associated with inflammatory bowel disease (IBD), which is characterized by persistent intestinal inflammation. Furthermore, the lifetime dietary choices of their host may positively or negatively affect both the gut microbiome and its impact on IBD. As such, “anti-inflammatory” dietary supplements, their impact, and mechanisms in restoring gut microbiota homeostasis during IBD is an area of intensive research. Dietary supplementation may represent an important adjuvant treatment avenue for limiting intestinal inflammation in IBD. Overall, this review addresses the development of the gut microbiome, the significance of the gut microbiome in IBD, and the use of dietary supplements such as vitamin D, fish oil, and resveratrol in the mitigation of IBD-associated gut dysbiosis and intestinal inflammation.

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