An Integrative View of Microbiome-Host Interactions in Inflammatory Bowel Diseases

Wlodarska, Marta; Kostic, Aleksandar D.; Xavier, Ramnik J.

doi:10.1016/j.chom.2015.04.008

Cited by 257 publications

(206 citation statements)

References 165 publications

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“…Unrestricted inflammation at intestinal sites leads to malabsorption of nutrients, severe abdominal pain, and increased chance of developing colorectal cancers (1). Although current therapies such as immunosuppression, intestinal resections, and antibiotics ameliorate symptoms, there is no cure for this disease.…”

Section: Introductionmentioning

confidence: 99%

A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice

et al. 2017

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The commensal microbiota has an important impact on host health, which is only beginning to be elucidated. Despite the presence of fungal, archaeal, and viral members, most studies have focused solely on the bacterial microbiota. Antibodies against the yeast Saccharomyces cerevisiae are found in some patients with Crohn’s disease (CD), suggesting that the mycobiota may contribute to disease severity. We report that S. cerevisiae exacerbated intestinal disease in a mouse model of colitis and increased gut barrier permeability. Transcriptome analysis of colon tissue from germ-free mice inoculated with S. cerevisiae or another fungus, Rhodotorula aurantiaca, revealed that S. cerevisiae colonization affected the intestinal barrier and host metabolism. A fecal metabolomics screen of germ-free animals demonstrated that S. cerevisiae colonization enhanced host purine metabolism, leading to an increase in uric acid production. Treatment with uric acid alone worsened disease and increased gut permeability. Allopurinol, a clinical drug used to reduce uric acid, ameliorated colitis induced by S. cerevisiae in mice. In addition, we found a positive correlation between elevated uric acid and anti-yeast antibodies in human sera. Thus, yeast in the gut may be able to potentiate metabolite production that negatively affects the course of inflammatory bowel disease.

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Section: Introductionmentioning

confidence: 99%

A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice

et al. 2017

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“…Bile acids are important regulators of the intestinal microbiota (21), which plays a crucial role in the pathogenesis of IBD (27). In order to examine the role of UDCA and its taurine-or glycine-conjugated species in the regulation of the intestinal microbiota D.…”

Section: Discussionmentioning

confidence: 99%

“…Considering that the gut microbial architecture and metabolism contribute to the course of IBD (27,28), we compared the therapeutic effectiveness of UDCA and its taurine or glycine conjugates in DSS-induced colitis in mice and investigated their impact on the fecal microbial community.…”

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confidence: 99%

Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice

Bossche

Hindryckx

Devisscher

et al. 2017

Appl Environ Microbiol

112

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The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes. Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD.IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we studied the alterations in the fecal microbial abundance in colitic mice following the administration of secondary bile acids. Our results show that secondary bile acids reduce the severity of colitis and ameliorate colitis-associated fecal dysbiosis at the phylum level. This study indicates that secondary bile acids might act as a safe and effective drug for inflammatory bowel disease.

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“…Les déséquilibres (ou dysbioses) du microbiote, qui peuvent être considérés comme des écarts par rapport à une composition moyenne, sont associés à de nombreuses maladies, comme par exemple, les maladies inflammatoires chroniques de l'intestin (MICI) [8]. Ainsi, il est aujourd'hui bien établi que l'homéostasie entre les composantes intestinales et microbiennes du tractus digestif est essentielle pour le maintien d'une bonne santé.…”

Section: Microbiote Immunité Santé Et Maladie : Un éQuilibre Essentunclassified

Lactobacillus acidophilus, un futur outil thérapeutique dans le traitement des maladies inflammatoires chroniques de l’intestin ?

Thomas

Langella

2015

Med Sci (Paris)

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An Integrative View of Microbiome-Host Interactions in Inflammatory Bowel Diseases

Cited by 257 publications

References 165 publications

A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice

A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice

Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice

Lactobacillus acidophilus, un futur outil thérapeutique dans le traitement des maladies inflammatoires chroniques de l’intestin ?

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