Lactobacillus salivarius MZ27 enhances the host's resistance to DSS by modulating the gut microbiota and the AHR/GPX4 signaling pathway.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose pathogenesis is related to dysbiosis and impaired immunity. Probiotics play an important role in alleviating IBD. This study aimed to investigate how Lactobacillus salivarius MZ27, isolated from disease-resistant Min pigs (a native Chinese pig breed), improved piglet colitis via aryl hydrocarbon receptor/glutathione peroxidase 4 (AHR/GPX4) signaling. We induced piglet colitis using dextran sulfate sodium (DSS), and the piglets were separated into the following four groups: CON, LAB, DSS, and DSS + LAB. The results showed that MZ27 can significantly alleviate diarrhea, bloody stools, and weight loss, reduce the content of myeloperoxidase (MPO) and D-lactate in colon tissue, increase colon length, and reduce goblet cell loss. Mechanistically, MZ27 can promote the production of indole-3-lactic acid (ILA) and short-chain fatty acids (SCFAs). This change may be associated with the increased relative abundance of Bifidobacterium and Prevotella; additionally, MZ27 can improve intestinal barrier function by regulating the expression of AHR and its downstream signaling pathways. Moreover, MZ27 inhibited ferroptosis by promoting GPX4 expression through AHR-mediated cystine-glutamate transporter (xCT) and toll-like receptor 4/acyl-CoA synthetase 4 (TLR4/ACSL4) signals, thereby reducing the release of inflammatory cytokines to alleviate colonic inflammation. In conclusion, MZ27 improves colitis through host-microbiota interactions, indicating its potential as a probiotic candidate to support recovery from ongoing colitis.