Intestinal dysbiosis exacerbates skin inflammation via microbial metabolite-driven Th2 cell differentiation - PubMed
5 hours ago
- #microbial metabolites
- #Th2 differentiation
- #gut-skin axis
- Intestinal epithelial TLR4 deficiency in mice leads to gut dysbiosis, exacerbating atopic dermatitis (AD).
- TLR4 deficiency reduces Akkermansia muciniphila and increases bacteria that convert choline to trimethylamine (TMA), raising TMAO levels in circulation.
- AD patients show higher plasma TMAO levels, correlating with disease severity and IgE; dietary choline intake is linked to increased AD risk in UK Biobank data.
- TMAO promotes Th2 cell differentiation by interacting with PPP5, which dephosphorylates PPARγ, and CD4+ T cell-specific PPARγ deletion prevents TMAO-driven skin pathology in mice.
- The study connects gut immune deficiency, microbial metabolites like TMAO, and skin inflammation, highlighting a gut-skin axis in AD pathogenesis.