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Probiotics as an effective and safe strategy for controlling  Salmonella  infection are much sought after, while autophagy is a central issue in eliminating intracellular pathogens of intestinal epithelial cells. In this study, an animal model of colitis has been developed by infecting weaned pigs orally with a strain of  Salmonella  Infantis in order to illuminate the potential efficacy of a mixture of  Lactobacillus  and  Bacillus  (CBB-MIX) in the resistance to  Salmonella  infection by regulating butyrate-mediated autophagy. We found that CBB-MIX alleviated  S . Infantis-induced colitis and tissue damage. Autophagy markers ATG5, Beclin-1, and the LC3-II/I ratio were significantly enhanced by  S . Infantis infection, while treatment with CBB-MIX suppressed  S . Infantis-induced autophagy. Additionally,  S . Infantis-induced colonic microbial dysbiosis was restored by this treatment, which also preserved the abundance of the butyrate-producing bacteria and the butyrate concentration in the colon. A Caco-2 cell model of  S . Infantis infection showed that butyrate had the same effect as the CBB-MIX in restraining  S . Infantis-induced autophagy activation. Further, the intracellular  S . Infantis load assay indicated that butyrate restricted the replication of cytosolic  S . Infantis rather than that in  Salmonella -containing vacuoles. Suppression of autophagy by knockdown of ATG5 also attenuated  S . Infantis-induced cell injury. Moreover, hyper-replication of cytosolic  S . Infantis in Caco-2 cells was significantly decreased when autophagy was inhibited. Our data demonstrated that  Salmonella  may benefit from autophagy for cytosolic replication and butyrate-mediated autophagy inhibition reduced the intracellular  Salmonella  load in pigs treated with a probiotic mixture of  Lactobacillus  and  Bacillus.

veterinary research

Butyrate-mediated autophagy inhibition limits cytosolic Salmonella Infantis replication in the colon of pigs treated with a mixture of Lactobacillus and Bacillus