Colonic Inhibition of Phosphatase and Tensin Homolog Increases Colitogenic Bacteria, Causing Development of Colitis in Il10-/- Mice

Abstract

Loss of Pten function increases the levels of colitogenic bacteria in the gut, thereby inducing deleterious colitis in an Il10-deficient condition.

Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon‐Soluble Capsule against Ulcerative Colitis

“…e phylogenetic analysis of microbiota associated with the administration of the different treatments revealed that Akkermansia was a distinct taxon in the DSS group. Additionally, counts of Akkermansia were reported to increase markedly after DSS administration and contributed to an increase in gut permeability, thus triggering IL-17 signaling and the release of IL-6 and IL-1β by myeloid cells [56]. In addition, Ruminococcaceae UCG-014 may be a key taxon in Crohn's Disease and UC and is associated with higher levels of proinflammatory cytokines in colitis models [25,57,58].…”

Autotaxin loss accelerates intestinal inflammation by suppressing TLR4‐mediated immune responses

“…Much in line with the role of IL-10 as an essential anti-inflammatory factor in gut mucosal immune responses, mice deficient in IL-10 spontaneously develop colitis in a gut microbe-dependent manner. Indeed, genetic defects of the IL-10 encoding gene cause aggressive intestinal inflammation in humans; therefore, mutation of the Il10 gene is a well-known genetic factor for IBD in humans (Glocker et al, 2009;Mitchell et al, 2018a). Accordingly, IL-10 mice are one of the most clinically relevant animal models of human IBD.…”

“…In this study, we identify an increased abundance of Bacteroides in the feces of Atx DΜΕ/DΜΕ ;Il10 À/À mice compared to that of Atx +/+ ;Il10 À/À littermates. The abundance of the Bacteroides genus is commonly increased in the feces of IL-10-ko mice with spontaneous colitis (Im et al, 2014;Mitchell et al, 2018a). Therefore, the elevated level of Bacteroides in Atx DΜΕ/DΜΕ ;Il10 À/À mice suggests that these mice are similarly experiencing chronic colitis as IL-10-ko mice do in a commensal microbe-dependent manner.…”

“…Inflammatory bowel diseases (IBD) is a chronic inflammatory disorder in the gut, which is caused by uncontrolled immune responses against commensal microbes in genetically susceptible individuals (Mitchell et al, 2018a). Previous studies have identified increased Atx mRNA expression in the inflamed colons of mice in which colitis was induced either by oral administration of dextran sulfate sodium (DSS) (Hozumi et al, 2013;Lin et al, 2019) or by adoptive transfer of CD4 + ;CD25 À T cells.…”

“…Elevated levels of the Bacteroides genus in the fecal microbiome are a commonly observed microbial manifestation of colitis in IL-10 signaling-defective mice (Bloom et al, 2011;Im et al, 2014;Mitchell et al, 2018a). In line with these studies, we observed through 16S rRNA gene sequencing that age-(8 weeks old) and sex-matched Atx DΜΕ/DΜΕ ; Il10 À/À and Atx +/+ ; Il10 À/À mice had distinct fecal microbiomes with elevated levels of the Bacteroides genus in Atx DΜΕ/-D ΜΕ; Il10 À/À (37.2%) mice compared to Atx +/+ ; Il10 À/À (14.3%, P = 0.0152) mice (Fig EV3A and B).…”