Prebiotics empower probiotics with gastrointestinal stress resistance for colon-targeted release to synergistically alleviate colitis

Abstract

Oral administration of probiotics holds promise for alleviating ulcerative colitis (UC), yet their efficacy is inevitably compromised by the hostile gastrointestinal (GI) environment. Here, we devised a strategy by coating β-glucan (GN) prebiotic onto the surface of Lactobacillus plantarum (Lp) probiotic at the single-cell level (Lp@CGN) based on bioorthogonal chemistry in a layer-by-layer manner. This achieved to form a firm, dense, and multifunctional GN-based “armor” with advances of superior protective properties, colon-targeted degradation, and prebiotic benefits. Under the protection of the prebiotic-based “armor”, Lp@CGN exhibited a notable 276-fold increase in the survival rate compared to naïve Lp after exposure to whole GI conditions. Upon reaching the colon, the “armor” was metabolized into short-chain fatty acids (SCFAs) by gut microbiota, facilitating the timely release of Lp within colon, thereby achieving a synergistic treatment effect due to sustained SCFAs generation and Lp liberation. As a result, oral administration of Lp@CGN efficiently realized the alleviation of UC in both preventative and therapeutic models through restoring intestinal mucosal barriers, positively regulating inflammatory cytokines, renovating the dysbiosis of gut microbiota, and promoting SCFAs production. In sum, our strategy marks the reconstruction of probiotics with chemical tools, offering useful insights into powering probiotics for disease treatment.