Resistant starch facilitates butyrate production by Bifidobacterium pseudolongum to mitigate colitis via Lgals4 upregulation

Dietary fiber’s capacity to support intestinal microbial homeostasis in mitigating disorders is well established. However, comparative studies on the mechanisms by which different dietary fibers bind to microbiota to alleviate intestinal inflammation remain insufficient. Therefore, the study investigated the association between gut microbiota and dietary fiber in the DSS-induced colitis model, and evaluated the potential mechanisms of specific microbiota and dietary fiber in managing this condition. The anti-inflammatory effects of three classical fibers with distinct digestive properties, including microcrystalline cellulose (MCC), resistant starch (RS), and inulin, were compared using a DSS-induced colitis model and single-cell RNA sequencing. Among them, RS showed superior efficacy, reducing the disease activity index and histopathological score relative to the fiber-free diet, and better restoring colonic crypts morphology than MCC and inulin. Mechanistically, RS alleviated inflammation by modulating IL-1β and Muc2 expression and markedly increasing Bifidobacterium pseudolongum and Bacteroides acidifaciens . Single-cell sequencing further revealed that RS promotes mucosal repair by upregulating epithelial Lgals4 , a carbohydrate-binding gene that activates intercellular junction pathways. Notably, co-supplementation of RS and B. pseudolongum provided additional protection. These findings indicate that B. pseudolongum plays a pivotal role in the pathogenesis of DSS-induced colitis treated with RS, offering significant insights for developing novel synbiotic strategies combining dietary fiber with probiotics. Furthermore, the synergistic effect between Bifidobacterium and RS in producing increased butyrate highlights the potential impact of probiotics and dietary fiber in suppressing the progression of colitis and other intestinal inflammations. Video Abstract