Inflammatory bowel disease microbiotas alter gut CD4 T-cell homeostasis and drive colitis in mice

Abstract

To examine the functional contribution of Inflammatory Bowel Disease (IBD) microbes to immune homeostasis and colitis, we colonized unchallenged and colitis-susceptible germ-free mice with over twenty human intestinal microbiotas from healthy and IBD donors. Compared to healthy microbiotas, IBD microbiotas led to expanded RORγt+Th17 cells and reduced RORγt+Treg in the gut of unchallenged gnotobiotic mice and increased disease severity in colitis-susceptible mice. The proportions of RORγt+Th17 and RORγt+Treg induced by each microbiota were highly predictive of the human disease status and strongly correlated with disease severity in colitis-susceptible mice colonized with the same human microbiotas. The transmittable functional potential of IBD microbes suggests a mechanism for a microbial contribution to IBD pathogenesis and a potential route for its treatment and prevention.

Polydopamine Nanoparticle‐Mediated Dopaminergic Immunoregulation in Colitis

“…[35] The abundances of Treg, Th1, Th2, and Th17 cells in LPMC were detected considering that their imbalance was linked with the progress of inflammation. [36] Mice without pretreatment with DSS and DSS mice dosed with phosphate buffered saline (PBS) were used as controls (Figure 3a). Apparently, PDNI increased the colonic length of the treated mice (Figure 3b,c).…”

Systemic IgG repertoire as a biomarker for translocating gut microbiota members

“…Bifidobacterium spp. have also been shown to cause small intestinal inflammation and pathology (52), and to induce large and small intestinal TH17 cells (53,54), a cell type implicated in human inflammatory bowel disease(55) as well as murine models (56). Not all translocator bacteria in our study exhibited comparative elevation of bacteriumspecific IgG in subjects for which translocation was confirmed.…”

Species-specific CD4+ T cells Enable Prediction of Mucosal Immune Phenotypes from Microbiota Composition

“…Microbial species such as Helicobacter and SFB are well characterized pathobionts that are known to both potentiate inflammation and also colonize healthy organisms (Chow and Mazmanian, 2010;Stepankova et al, 2007). In addition, stools from human IBD gut microbiotas induce more severe colitis in susceptible mice compared to healthy donor microbiotas despite no discernable differences in terms of composition and diversity (Britton et al, 2019). Determining how microbial organisms exist harmoniously in some contexts but increase the risk for inflammation in others is a fundamental question for the microbiome field.…”

“…Gut tissues were prepared as previously described (Britton et al, 2019). Briefly, cleaned gut tissues were deepithelialized in 5 mM ethylenediaminetetraacetic acid (EDTA), 15 mM Hepes, and 5% fetal bovine serum (FBS) in Hank's Balanced Salt Solution (HBSS) before digestion with 0.5 mg/mL Collagenase Type IV (Sigma Aldrich) and 0.25 mg/mL DNase 1 in HBSS with 2% FBS.…”