A secondary metabolite of Limosilactobacillusreuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis.

Limosilactobacillus reuteri is an immunomodulatory bacterium enriched in non-industrialized microbiomes, making it a therapeutic candidate for chronic diseases. However, effects of L. reuteri strains in mouse models of multiple sclerosis have been contradictory.

The Pregnane X Receptor and Indole-3-Propionic Acid Shape the Intestinal Mesenchyme to Restrain Inflammation and Fibrosis.

Background & Aims: Fibrosis is a common complication of inflammatory bowel diseases (IBDs). The pregnane X receptor (PXR) (encoded by NR1I2) suppresses intestinal inflammation and has been shown to influence liver fibrosis. In the intestine, PXR signaling is influenced by microbiota-derived indole-3-propionic acid (IPA).

Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood.

Xenobiotic receptors and the regulation of intestinal homeostasis: harnessing the chemical output of the intestinal microbiota.

The commensal bacteria that reside in the gastrointestinal tract exist in a symbiotic relationship with the host, driving the development of the immune system and maintaining metabolic and tissue homeostasis in the local environment. The intestinal microbiota has the capacity to generate a wide array of chemical metabolites to which the cells of the intestinal mucosa are exposed. Host cells express xenobiotic receptors, such as the aryl hydrocarbon receptor (AhR) and the pregnane X receptor (PXR), that can sense and respond to chemicals that are generated by nonhost pathways.

The xenobiotic sensing pregnane X receptor regulates tissue damage and inflammation triggered by C difficile toxins.

Clostridioides difficile (formerly Clostridium difficile; C difficile), the leading cause of nosocomial antibiotic-associated colitis and diarrhea in the industrialized world, triggers colonic disease through the release two toxins, toxin A (TcdA) and toxin B (TcdB), glucosyltransferases that modulate monomeric G-protein function and alter cytoskeletal function. The initial degree of the host immune response to C difficile and its pathogenic toxins is a common indicator of disease severity and infection recurrence. Thus, targeting the intestinal inflammatory response during infection could significantly decrease disease morbidity and mortality.

The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent vasodilation.

We proposed that circulating metabolites generated by the intestinal microbiota can affect vascular function. One such metabolite, indole 3-propionic acid (IPA), can activate the pregnane X receptor(PXR), a xenobiotic-activated nuclear receptor present in many tissues, including the vascular endothelium. We hypothesized that IPA could regulate vascular function by modulating PXR activity.