Browsing by Author "Nieves, Kristoff Michael"

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    Intestinal Homeostasis: The role of Indole-3-propionic acid (IPA) in mucosal homeostasis and repair
    (2020-05) Nieves, Kristoff Michael; Hirota, Simon Andrew; Geuking, Markus B.; Lu, Cathy; von der Weid, Pierre Yves; Chadee, Khrisendath
    Failure to resolve inflammation is often associated with the complications of Crohn’s Disease (CD). The pregnane X receptor (PXR), a xenobiotic receptor, is recognized for its role in suppressing inflammation and has recently been shown to influence fibrogenesis in the liver. In the intestine, PXR-signaling can be influenced by the microbial tryptophan metabolite indole-3- propionic acid (IPA), which can modulate intestinal inflammation, in turn influencing fibrogenesis, resolution and healing. This suggests that the gut microbiota could modulate mucosal homeostasis and resolution of inflammation via microbial metabolites. We therefore hypothesized that the microbial metabolite IPA through its activation of the PXR would act as a negative regulator of fibrosis. Using a gnotobiotic mouse model revealed, contrary to our hypothesis that activation of the PXR with the microbial metabolite IPA did not attenuate fibrosis. However, IPA did increase survival in the gnotobiotic mice to DSS-induced colitis. Additionally, fecal microbiota composition analysis revealed that IPA induces protection against the depletion of commensal Bacteroides spp. induced by DSS. Taken together, this data provides a foothold of knowledge into the relationship between the microbiota and host and highlights the potential for alternative means of the treatment of IBD and its complications.