Different intestinal ecological niches drive the divergent evolution of probiotics in the gut

Abstract Previously, we described the divergent evolution of probiotics in the gut, which potentially compromises their health-promoting effects. Here, we employed a spatiotemporal multiomic approach to explore the distribution and evolutionary trends of the probiotic Lactiplantibacillus plantarum HNU082 (Lp082) in specific-pathogen-free and monocolonized mouse models. Initially, after establishing the inherent differences in the gut microbiota between the small and large intestines, we observed that the small intestine served as the main site for Lp082 survival and colonization. Subsequently, we discovered that the small intestine was the sole site where Lp082 exhibited divergent evolution. Moreover, our research indicated that Lp082 had a more substantial impact on the small-intestinal microbiota than on the large-intestinal microbiota. Consequently, we observed a significantly greater number of closely associated species coevolving with Lp082 in the small intestine than in the large intestine. This suggests that Lp082 faced higher selective pressures within the small intestine, potentially leading to the emergence of a greater number of mutants. Our findings will contribute to the differentiated application of probiotics, enhancing their beneficial effects, and offer insights into the targeted domestication of probiotic strains.