Transplanting beneficial bacteria to the gut microbiome can positively modulate the bacterial composition and remains of great interest in prevention and treatment. However, environmental assaults and rapid transit times in the gastrointestinal (GI) tract result in low oral bioavailability and limited intestinal colonization. Here, we describe a bioinspired strategy of self-coating with biofilms that endows the transplanted gut microbiota with superior resistance and adhesion capacity. Using clinical Bacillus subtilis as a model probiotic bacterium, biofilm-coated probiotics demonstrate substantially improved GI tract tolerance and mucoadhesion in mice and swine. In particular, coated probiotics exhibit a 125-fold higher oral bioavailability and a 17 times greater intestinal colonization than uncoated bacteria in the porcine model. With notable ability to survive and reside in the GI tract, coated bacteria further show a significantly enhanced decolonization effect in mice colonized with Staphylococcus aureus. Self-coating with biofilms suggests a robust platform for oral doses of gut microbiota.

Outer membrane vesicles (OMVs) play vital roles in bacterial communication both intraspecifically and interspecifically. However, extracellular mechanisms of gut microbiota–derived OMVs in the intestine remain poorly understood. Here, we report that OMVs released from Akkermansia muciniphila are able to (i) restore disturbed balance of the gut microbiota by selectively promoting the proliferation of beneficial bacteria through membrane fusion, (ii) elicit mucosal immunoglobulin A response by translocating into Peyer’s patches and subsequently activating B cells and dendritic cells, and (iii) maintain the integrity of the intestinal barrier by entering intestinal epithelial cells to stimulate the expressions of tight junctions and mucus. We demonstrate that transplantation of gut microbiota–associated OMVs to the intestine can alleviate colitis and enhance anti–programmed cell death protein 1 therapy against colorectal cancer by regulating intestinal homeostasis. This work discloses the importance of gut microbiota–derived OMVs in intestinal ecology, providing an alternative target for disease intervention and treatment.