Colon-targeted and adhesion-colonized Weizmannia coagulans-procyanidins delivery system intervene in ulcerative colitis and its associated anxiety and depression via gut-microbiota-brain axis

A colon-targeted and adhesion-colonized BC99 and PC co-delivery system was prepared. • Microgels with high embedding rate could effectively maintain the survival rate of BC99. • Microgels improved the mechanical, immune and microbial barriers in UC mice. • Microgels improved the levels of brain neurotransmitters and metabolites. • Gut-microbiota-brain axis is an important pathway to alleviate UC and its comorbidities. Two-way communication between gut and brain can cause people with ulcerative colitis (UC) to exhibit notable mental disorders, such as anxiety and depression. In this study, Weizmannia coagulans BC99 and procyanidins co-delivery systems with adhesive colonization and colon targeting functions was prepared, and the mechanism for alleviating colitis and its accompanying anxiety-depression symptoms was revealed by regulating gut-microbiota-brain axis. The prepared microgels were spherical with 95.18% encapsulation efficiency, and could effectively maintain the survival rate of probiotics under simulated digestion conditions. The microgel also had mucosal adhesion, colon targeting and intestinal colonization capabilities. Subsequently, a UC mouse model was constructed, and the colon length of mice increased by 41.42% after SH-BP@PWC microgel intervention. SH-BP@PWC effectively inhibited the degree of oxidative stress, reduced the release of pro-inflammatory cytokines, maintained the mechanical barrier integrity of gut, regulated the imbalance of gut microbiota and arginine biosynthesis pathway. Moreover, the microgel could effectively relieve anxiety and depression-like behaviors in UC mice, improve the level of brain neurotransmitters, and relieve depressive symptoms by regulating metabolites, such as arginine. Correlation analysis further proved the interactions among gut microbiota, oxidative stress, inflammatory cytokines, brain neurotransmitters, and metabolites, highlighting the central role of gut-microbiota-brain axis, especial arginine metabolic pathway. This study designs a probiotic multifunctional co-delivery system that can provide new insights into alleviating colitis and its accompanying anxiety and depression from gut-microbiota-brain axis. A colon-targeted and adhesion-colonized Weizmannia coagulans -procyanidins delivery system was successfully designed and prepared, which could effectively alleviate colitis and its accompanying anxiety and depression via gut-microbiota-brain axis. Download: Download high-res image (211KB) Download: Download full-size image