Berberine alleviates radiation-induced lung injury through promoting microbiota-derived inosine via gut-lung axis

Radiation-induced lung injury (RILI) is a major complication of thoracic radiotherapy. A previous study has indicated an association between berberine (BBR) and reduced incidence of RILI. However, the underlying mechanisms remain unknown. Here we validated the radioprotective role of BBR in mouse model, and we found that this effect was due to gut microbiota modulation as evidenced by microbiota depletion and fecal microbiota transplantation. Specifically, BBR treatment enriched the abundance of Akkermansia muciniphila in gut and its metabolite, inosine (INO). INO exerted protective effects against RILI via epigenetic regulation of NAV3 through H3K27me3 modification. Our findings suggest the potential of BBR in developing therapeutic strategies for RILI and provides insights into its radioprotection mechanism. Additionally, INO could serve as a complementary approach to enhance radioprotection in RILI.