Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice

Abstract

Studying host-microbiota interactions are fundamental to understanding the mechanisms involved in intestinal homeostasis and inflammation. In this work, we analyzed these interactions in mice that were mono-associated with six microorganisms that are representative of inflammatory bowel disease (IBD)-associated dysbiosis: the bacteria Bacteroides thetaiotaomicron, adhesive-invasive Escherichia coli (AIEC), Ruminococcus gnavus and Roseburia intestinalis; a yeast used as a probiotic drug, Saccharomyces boulardii CNCM I-745; and another yeast, Candida albicans. Extensive ex vivo analyses including colon transcriptomics, histology, immune response, bile acid metabolism and short-chain fatty acid production were studied. We showed that B. thetaiotaomicron had the highest impact on the immune system because it was almost able to recapitulate the effects of the entire conventional microbiota and notably induced Treg pathways. Furthermore, these analyses uncovered the effects of E. coli AIEC LF82 on indoleamine 2,3-dioxygenase expression and of S. boulardii CNCM I-745 on angiogenesis. These results were confirmed in vitro in human cell lines. Finally, our results suggested that R. gnavus has major effects on metabolism, and notably on tryptophan metabolism. This work therefore reveals that microorganisms with a potential role in intestinal homeostasis and inflammation have specific impacts on the host, and it suggests several tracks to follow to understand intestinal homeostasis and IBD pathogenesis better, providing new insights to identify novel therapeutic targets.

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease

“…Comparative analysis using the weighted UniFrac distance indicated that the difference between CD and non-IBD controls was more marked than that between UC and non-IBD controls. These observations are compatible with the results of previous studies of fecal samples [33,34]. A focal alteration of the microbial structure within the inflamed mucosa of IBD has been reported previously [35].…”

“…These results are consistent with those of previous reports of fecal samples [1,3,4]. The pathological role of the genus Escherichia has been shown in many studies of adhesive-invasive E. coli [3,4,33], and R. gnavus has been reported to contribute to the pathophysiology of IBD through its mucolytic activity [35]. The genera Faecalibacterium, Coprococcus and Roseburia are the main butyrate-producing bacteria belonging to the order Clostridiales [36,37], and play a beneficial role in maintaining gut health.…”

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

“…Ruminococcus exerts pro-inflammatory effects and contributes to inflammatory bowel disease (IBD) pathogenesis [28]. Ruminococcus transplantation in germ-free mice enhances interferon-γ, interleukin 17, and interleukin 22 amounts [29]. Dialister was shown to be associated with antepartum preeclampsia samples [30].…”

Quantitative Risk–Benefit Analysis of Probiotic Use for Irritable Bowel Syndrome and Inflammatory Bowel Disease

“…(7) Given the abovementioned disorders' association with dysregulation of the human microbiome, interest has mounted in the use of probiotics to treat both irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). While dysbiosis remains a likely, (12)(13)(14) but as yet poorly understood mechanism for IBD and IBS, this has not stunted the a priori assumption by many clinicians and patients that probiotics may be helpful.…”

“…While their etiologies are unknown, they are both likely related to a dysregulated interaction between the normal intestinal microbiota and the host immune system. (12,13) Probiotics have been difficult to study (3), largely because they defy typical drug classification in many settings:…”