Gut microbial metabolite urolithin B attenuates intestinal immunity function in vivo in aging mice and in vitro in HT29 cells by regulating oxidative stress and inflammatory signalling

Abstract

Urolithin B (Uro B), one of the major subcategories of urolithins (microbial metabolites) found in various tissues after ellagitannin consumption, has been demonstrated to possess antioxidant and anti-inflammatory effects. The current research mainly focused on the ameliorative effect of Uro B on intestinal immunity function and exploring the potential mechanisms of its protective role in aging mice induced by D-galactose (D-gal). In the current research, we assessed the ameliorative effects of Uro B on inflammatory injury induced by lipopolysaccharides in HT29 cells. The D-gal-induced accelerated aging model in vivo demonstrated that Uro B could elevate the activities of superoxide dismutase, catalase, glutathione peroxidase, and total anti-oxidation capability, decrease malondialdehyde content, regulate the levels of inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-4, and IL-1β) in the small intestine, and reshape the composition of gut microbiota and decrease the intestinal barrier injury in aging mice. Furthermore, Uro B inhibited the expression of TLR4, IRAK4, TRAF6, IKK-β, NF-κB p65, and HMGB1 in the small intestine. Therefore, these findings indicated that Uro B effectively weakened the injury to the small intestine and ameliorated intestinal immunity function through the downregulation of the HMGB1-TLR4-NF-κB pathway in aging mice. Uro B could be considered a healthcare product to prevent diseases associated with an aging immune system.