Zhengrong Zhou, Siyu Wang, Kangping Shao, Mingzi Qu, Xin Qian, Genbao Shao, Jianpeng Hu, Guohong Qiao, Pan Huang
L-lactate, a byproduct of glycolysis and hypoxia, accumulates in the gut during disease progression and may affect host responses and microbial metabolism. Here, we investigated the protective effect of sodium L-lactate on dextran sulfate sodium (DSS)-induced colitis in mice and the involvement of the gut microbiota. Oral sodium L-lactate significantly alleviated colitis, as shown by reduced body weight loss, fecal occult blood score, colon shortening, and histological injury. It also improved mucus secretion and intestinal barrier integrity, decreased serum IL-6, and increased IL-10. In specific pathogen-free mice, fecal lactate did not accumulate after sodium L-lactate administration, whereas marked accumulation was observed in antibiotic-treated mice, suggesting active microbial utilization of exogenous lactate in vivo. Antibiotic treatment weakened the protective effect of sodium L-lactate, while fecal microbiota transplantation from treated donors transferred protection to recipient mice. Gut microbiota analysis showed that sodium L-lactate reshaped the microbial community and consistently enriched Akkermansia. Oral administration of Akkermansia alone also ameliorated DSS-induced colitis. Together, these findings indicate that sodium L-lactate alleviates intestinal inflammation at least partly through gut microbiota modulation and highlight its potential as a functional strategy for gut health.