Baicalin inhibits APEC-induced lung injury by regulating gut microbiota and SCFAs production

Baicalin is a plant-derived flavonoid from Scutellaria baicalensis Georgi with multiple bioactivities and has showed a protective effect against avian pathogenic Escherichia coli (APEC) infection. However, the underlying mechanism of baicalin against APEC infection is still unknown. Therefore, we aimed to explore whether the protective effects and mechanisms of baicalin on APEC-induce lung inflammation by regulating gut microbiota. The results showed that baicalin protected against APEC infection with evidences including reduced APEC colonization, pro-inflammatory cytokines production, and recovered air-blood barrier integrity. However, depletion of gut microbiota weakened the protective effects of baicalin on APEC infection as mentioned above. Furthermore, baicalin restored the dysbiosis of gut microbiota induced by APEC and increased the abundance of short chain fatty acids (SCFAs)-producing bacteria and the production of SCFAs including acetate, propionate and butyrate especially acetate. In addition, the concentration of acetate and its receptor free fatty acid receptor 2 (FFAR2) were significantly up-regulated in lung tissues after baicalin treatment. In conclusion, gut microbiota played a protective role in the pharmacological action of baicalin against APEC-induced lung inflammation. Furthermore, baicalin remodeled the dysbiosis of gut microbiota caused by APEC and increased production of SCFAs especially acetate in gut. The increased acetate may circulate to the lung to activated FFAR2 to defend APEC infection. Together, our study suggested baicalin significantly inhibited APEC infection by regulating the gut microbiota and increasing the SCFAs production. Further, baicalin may serve as alternative antibiotics, novel therapeutic drug to prevent or treat APEC infection.