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• W2890880346 abstract "Microbiome-derived metabolites influence intestinal homeostasis and regulate graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown. Here we show the metabolite sensor G-protein-coupled receptor 43 (GPR43) is important for attenuation of gastrointestinal GVHD in multiple clinically relevant murine models. GPR43 is critical for the protective effects of short-chain fatty acids (SCFAs), butyrate and propionate. Increased severity of GVHD in the absence of GPR43 is not due to baseline differences in the endogenous microbiota of the hosts. We confirm the ability of microbiome-derived metabolites to reduce GVHD by several methods, including co-housing, antibiotic treatment, and administration of exogenous SCFAs. The GVHD protective effect of SCFAs requires GPR43-mediated ERK phosphorylation and activation of the NLRP3 inflammasome in non-hematopoietic target tissues of the host. These data provide insight into mechanisms of microbial metabolite-mediated protection of target tissues from the damage caused allogeneic T cells." @default.
• W2890880346 created "2018-09-27" @default.
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• W2890880346 date "2018-09-10" @default.
• W2890880346 modified "2023-10-10" @default.
• W2890880346 title "Microbial metabolite sensor GPR43 controls severity of experimental GVHD" @default.
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• W2890880346 doi "https://doi.org/10.1038/s41467-018-06048-w" @default.
• W2890880346 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6131147" @default.
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• W2890880346 hasPublicationYear "2018" @default.
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