Silk Fibroin Enhances Probiotic-driven Malic Acid Production to Alleviate Colitis

Inflammatory bowel disease (IBD) is a chronic intestinal disorder with a rapidly increasing global incidence, for which current therapies often fail to fully restore epithelial barrier integrity and gut microbiota homeostasis. Here, we report a silk fibroin (SF)-enabled probiotic strategy that alleviates colitis by modulating gut microbial metabolism. A bioactive SF nanocoating was applied to Escherichia coli Nissle 1917 (EcN), enhancing probiotic survival and intestinal colonization while providing additional anti-inflammatory and microbiota-regulatory functions. In a dextran sulfate sodium (DSS)-induced murine colitis model, the SF-coated probiotic markedly attenuated intestinal inflammation and promoted epithelial barrier repair compared with SF or EcN alone. Mechanistically, SF treatment selectively enriched Bacteroides acidifaciens, leading to increased production of the microbiota-derived metabolite malic acid. Functional analyses demonstrated that malic acid facilitates epithelial regeneration and barrier restoration, at least in part, through activation of intestinal Wnt/beta-catenin signaling. Together, these findings identify a material-enabled microbiota-metabolite-host signaling axis underlying the therapeutic efficacy of this approach, and highlight the potential of functional biomaterials to reshape gut microbial metabolism for IBD treatment.