Native microbiome dominates over host factors in shaping the probiotic genetic evolution in the gut

Abstract Probiotics often acquire adaptive mutations in vivo gaining new functional traits through gut selection. However, it remains challenging to separate microbiome and host contribution to such selective pressures. Here, we tracked and compared the temporal genetic evolution of representative probiotic strains in germ-free (GF) and specific-pathogen-free (SPF) mice. Notably, host only elicited < 15 probiotic mutations, < 0.25% of those derived from both factors that was never captured by other experimental evolution studies, indicating that keen microbial competitions exhibited the predominant evolutionary force in shaping probiotic genetic composition (> 99.75%). Furthermore, native microbiome consistently drove a more rapid and divergent genetic evolution of probiotic strains in seven days of colonization than host factors did. Our study further laid a theoretical foundation for genetically engineering probiotics for better gut adaptation through in vitro artificial gut ecosystems without the selection pressures derived from host factors.