ABSTRACT Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven by microbial dysbiosis, barrier dysfunction, and immune dysregulation. Given the limitations of current therapies, we evaluated the probiotic potential of Lactobacillus plantarum NCU001563 (LP) in a mouse model of dextran sulfate sodium (DSS) ‐induced UC. LP treatment markedly alleviated disease severity, reducing weight loss, colon shortening, and histological damage. It restored immune balance by decreasing proinflammatory mediators (TNF‐α, IL‐6, IL‐1β, MPO, IgE) and increasing anti‐inflammatory cytokines (IL‐10, TGF‐β2) via modulation of the JAK‐STAT and Smad2 signaling pathways. LP also reversed microbial dysbiosis, reducing pathogenic genera, such as Clostridiumₛensuₛtricto₁, Escherichia‐Shigella, and Turicibacter, while enriching beneficial genera like Muribaculaceae, LachnospiraceaeNK4A136group, Odoribacter, Blautia, and Ruminiclostridium₉. Metabolomic analysis revealed that LP suppressed proinflammatory pathways (arachidonic acid metabolism) and proinflammatory metabolites (LysoPEs), while upregulating amino acid biosynthesis and enriching anti‐inflammatory metabolites (caffeoyl aspartic acid and armillarivin). Mechanistically, these changes were linked to the inhibition of the JAK‐STAT pathway and the activation of the TGF‐β2/Smad2/IL‐10 axis. These findings demonstrated that LP possesses a protective response via the microbiota–metabolite–immune axis, positioning it as a promising next‐generation probiotic for UC management.
Madjirebaye et al. (Sun,) studied this question.