Comparative genomics and single-cell transcriptomics reveal the ecological adaptation strategies of lactobacillus with different lifestyles

Lactobacilli with different lifestyles show different ecological adaptabilities and host interaction abilities in the intestine. This study conducted a comparative genome analysis of 232 strains of lactobacilli, combined with carbohydrate-active enzyme and colonization factor analysis, and found that the genome of free-living lactobacilli is larger than that of host-adapted lactobacilli and the CAZymes spectrum is closely related to its lifestyle. In vivo experiments showed that host-adapted lactobacilli have significantly better colonization ability in the intestine than nomadic lactobacilli, and can still maintain a high number of live bacteria after stopping intake. Single-cell transcriptome technology was further used to explore the effects of lactobacilli intake on intestinal cells from the host perspective, and it was found that epithelial cells and immune cells (especially T cells and B cells) were most significantly affected by lactobacilli. Specifically, host-adapted lactobacilli (such as Lactobacillus reuteri) showed stronger anti-inflammatory effects in regulating Cd4+Tn cells, Cd4+Th/Treg cells, and Cd8ααT cells, and significantly downregulated the differentiation of pro-inflammatory cells such as Th1, Th2, and Th17. These findings not only clarify the relationship between Lactobacillus lifestyle and its genomic characteristics, colonization ability and immunomodulatory function, but also provide an important theoretical basis for the formulation of precise probiotic intervention strategies based on Lactobacillus.