<i>Bacteroides thetaiotaomicron</i>Ameliorates Colon Inflammation in Preclinical Models of Crohn’s Disease

Delday, Margaret Inkster; Mulder, Imke; Logan, Elizabeth; Grant, George

doi:10.1093/ibd/izy281

Cited by 138 publications

(122 citation statements)

References 58 publications

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“…The importance of regulatory IL-10 to the healthy response of DC to Bt OMVs is congruent with observations in mice showing that Bt is colitogenic in dnKO mice lacking IL-10 and TGFb-signalling pathways 10,24 . Conversely, a strain of Bt different to that used in our study was shown to protect otherwise susceptible IL-10R-deficient mice or dextran sodium sulfate-treated mice and rats from developing colitis 11 . These discrepancies support the proposal that Bt protective functions are, at least in mice, not limited to IL-10-related pathways and may be dependent on environmental, bacterial strain-and host-specific factors 69 .…”

Section: Discussionmentioning

confidence: 58%

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

Durant

Stentz

Noble

et al. 2020

Preprint

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Background: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all Gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn’s disease (CD) or ulcerative colitis (UC). Results: In healthy individuals, Bt OMVs stimulated significant (p<0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p<0.001 and p<0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103+ DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p<0.01 and p<0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). Conclusions: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients.

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Section: Discussionmentioning

confidence: 58%

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

Durant

Stentz

Noble

et al. 2020

Preprint

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“…Moreover, MV also significantly increased the abundance of B. ovatus in our study (Figure G). A closely related species, B. thetaiotaomicron , has been shown to ameliorate colon inflammation in two different IBD models including DSS model . Cumulatively, evidence suggests that the metabolites of MV metabolism are conducive to host health by enhancing growth of beneficial bacteria in the gut …”

Section: Discussionmentioning

confidence: 99%

Malvidin 3‐Glucoside Modulated Gut Microbial Dysbiosis and Global Metabolome Disrupted in a Murine Colitis Model Induced by Dextran Sulfate Sodium

Liu

Wang

Tang

et al. 2019

Molecular Nutrition Food Res

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Scope: This study aims to elucidate the mechanisms of the anthocyanin malvidin 3-glucoside (MV) in alleviating gut dysbiosis using a murine colitis model induced by dextran sulfate sodium (DSS). Methods and results: The effect of MV on the structure and function of the colon microbiome and microbial metabolism is evaluated using 16S rRNA gene sequencing, global metabolomics, and a network algorithm based on the random-matrix theory. MV ingestion improved histopathological scores and increased IL10 expression in the colon mucosa of colitis mice. While DSS has a profound effect on the gut microbiome and significantly decreases both microbial richness and evenness, MV further reduces evenness but promotes microbial interactions and restores the Firmicutes/Bacteroidetes ratio repressed by DSS. Moreover, MV reduces the abundance of pathogenic bacteria, such as Ruminococcus gnavus, in colitis mice and has a strong modulatory effect on microbial co-occurrence patterns and gut metabolites. In addition, MV reverses several key inflammatory mediators, including sphingolipid metabolites, from elevated levels in DSS colitis mice. As a bioactive ingredient, MV exerts its effect on the gut microbiome in a mechanism that differs from the whole blueberry. Conclusion: MV ingestion ameliorates intestinal inflammation by modulating colon epithelium integrity, gut microbiome, and key inflammatory mediators.

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“…Bacteroides thetaiotaomicron is an acetate producer that promotes goblet cell differentiation and mucus production, ultimately providing protection against intestinal inflammation by strengthening the gut barrier (89). Recently, additional studies suggested B. thetaiotaomicron colonization demonstrated therapeutic properties in preclinical models of CD (90), although separate studies showed that B. thetaiotaomicron can be pathogenic in patients with certain genetic susceptibilities (75,91). Finally, alterations to bacterial colonization can lead to downstream metabolic or indirect effects on other bacteria.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity

2020

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There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characterizes Multiple Sclerosis. Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier. In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.

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Bacteroides thetaiotaomicronAmeliorates Colon Inflammation in Preclinical Models of Crohn’s Disease

Cited by 138 publications

References 58 publications

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

Malvidin 3‐Glucoside Modulated Gut Microbial Dysbiosis and Global Metabolome Disrupted in a Murine Colitis Model Induced by Dextran Sulfate Sodium

Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity

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