<i>Lactobacillus Plantarum 6C</i> Alleviates DSS‐Induced Colitis via  <i>Ligilactobacillus</i>  Enrichment‐Dependent Suppression of the PI3K‐AKT Signaling Pathway

ABSTRACT Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex pathogenesis. Previous studies have shown that probiotics alleviate UC by modulating the gut microbiome. Therefore, this study aimed to investigate the ameliorative effect of Lactobacillus plantarum 6C ( L. plantarum 6C) on dextran sulfate sodium (DSS)‐induced UC mice and to elucidate its specific mechanism. The results showed that L. plantarum 6C intervention ameliorated DSS‐induced UC in mice, as evidenced by reduced colon shortening and weight loss, diminished levels of the pro‐inflammatory cytokine IFN‐γ, and increased the levels of the anti‐inflammatory cytokine IL‐4. Additionally, L. plantarum 6C reduced oxidative stress markers (MPO and MDA levels), enhanced the protein expression of E‐cadherin, occludin, and ZO‐1, and increased the abundance of beneficial bacteria such as Ligilactobacillus , Prevotella , and Dysosmobacter . Furthermore, L. plantarum 6C upregulated the Lama2 and Lamb2 genes, which are key genes in the PI3K‐AKT pathway. In conclusion, our results indicate that L. plantarum 6C ameliorates DSS‐induced colitis, its potential mechanism may be the increased abundance of Ligilactobacillus , which modulates Lama2 and Lamb2 expression, thereby suppressing the PI3K‐AKT signaling pathway. Overall, this study demonstrates the beneficial role of L. plantarum 6C in alleviating ulcerative colitis and promoting intestinal homeostasis.