Postbiotics ameliorate DSS-induced colitis in mice by regulating gut microbiota, promoting tryptophan metabolism, and activating AhR/ IL-22 signaling pathway

Abstract

Inactivated probiotics, due to their high safety, effectiveness, stability, and resilience, are increasingly used for treating various diseases. To assess the efficacy of inactivated Bifidobacterium bifidum M1-3 in alleviating dextran sulfate sodium salt (DSS) -induced colitis, we compared the effects of live probiotics and inactivated probiotics at different concentrations on colitis in male C57BL/6J mice. Additionally, we explored potential mechanisms by analyzing changes in gut microbiota composition, tryptophan metabolites, and the AhR/IL-22 signaling pathway. Our study demonstrated that administering high doses (2 × 10⁹ CFU/mL) of heat-inactivated probiotics by gavage for 14 days effectively alleviated DSS-induced colitis in mice, with effects comparable to those of live probiotics. This effect was attributed to the modulation of gut microbiota, with an increase in beneficial bacteria like Muribaculaceae, Alistipes, and Ruminococcaceae, and a reduction in harmful microbes such as Escherichia/Shigella spp. Additionally, the inactivated probiotics enhanced tryptophan metabolism, leading to elevated levels of metabolites including indole-3-lactic acid, indole-3-propionic acid, indole acrylic acid, and indole, which subsequently activated the AhR/IL-22 signaling pathway. Our results confirmed the effectiveness of heat-inactivated Bifidobacterium bifidum M1-3 in alleviating colitis, demonstrating a dose-dependent response. The soluble capsular polysaccharides in the bacterial lysate supernatant are the potentially effective components of Bifidobacterium bifidum M1-3. This finding provides a theoretical basis for developing novel probiotic products containing heat- inactivated Bifidobacterium bifidum M1-3.