Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by compromising the mucosal barrier

Abstract Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury (ARIII). However, studies on the influence of gut microbiota on ARIII are inconsistent. In this study, we established an ARIII mouse model and performed fecal microbiota transplantation (FMT) to explore the role of the gut microbiota in ARIII. We observed a significant increase in Akkermansia muciniphila (AKK) following irradiation, whereas FMT effectively reduced AKK levels. Contrary to expectations, AKK supplementation increased ARIII and mortality. Mechanistically, post-radiation AKK upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating ARIII. This enables AKK to use mucin as an energy source. Additionally, AKK increases the infiltration of M1-type macrophages and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating ARIII. Our findings suggest that in certain intestinal environments, the addition of AKK may worsen radiation-induced intestinal damage; thus, the potential of AKK as a universal probiotic should be considered with caution.