Toward clinical translation: montmorillonite-enhanced Lactobacillus biofilm alleviates colitis by modulating the gut microbiota–bile acid axis

Oral probiotics hold therapeutic potential for ulcerative colitis (UC), but their low bioavailability greatly limits clinical efficacy. Here, we designed a montmorillonite– Lactobacillus acidophilus biofilm (MLB) delivery strategy to enhance probiotic stability, intestinal adhesion, and therapeutic efficiency. MLB was prepared by inducing the clinically common strain Lactobacillus acidophilus to form biofilms on montmorillonite, an antidiarrheal agent widely used in clinics. The in vitro assays demonstrated that montmorillonite significantly promoted biofilm formation, thereby improving bacterial survival in gastrointestinal conditions and enhancing mucosal adhesion. In vivo, MLB showed superior efficacy in alleviating DSS-induced colitis compared with free bacteria or non-biofilm mixtures. Mechanistically, MLB remodeled gut microbiota composition and restored microbial bile acid metabolism through elevated bile salt hydrolase activity. This led to increased production of secondary bile acids, which in turn promoted anti-inflammatory macrophage polarization and facilitated inflammation resolution. Together, these findings demonstrate that MLB enhances the efficacy of oral probiotics by targeting the microbiota–bile acid–immune axis, representing a safe and practical approach for UC treatment. Graphical abstract: The preparation, enhanced oral delivery, and therapeutic mechanism of MLB. (A) Genetic evidence indicates a causal relationship between reduced Lactobacillus abundance and increased risk of UC. (B) The preparation of MLB. (C) Oral delivery of the MLB and their therapeutic mechanism in treating UC.