Abstract
The gut microbiome plays a central role in human health, but modern diets and lifestyles alter its composition. The microbial genomic traits that drive these ecological shifts, particularly in response to dietary sugars, remain poorly characterized. Here, we integrate a large dataset of longitudinal human diet-microbiome records and comparative genomics of human and murine gut isolates with in vitro and in vivo experiments to identify sugar ABC (ATP-binding cassette) transporters as key predictors of bacterial fitness and microbial community responses to dietary sugars. Strains encoding these transporters exhibit enhanced growth and consistently outcompete others in both monocultures and complex consortia across contexts. In gnotobiotic mice, dietary sugar supplementation selectively increases the expansion of sugar ABC transporter-positive bacteria, including the model gut pathobiont Escherichia coli . Systematic deletion of sugar transporter genes in E. coli revealed that a specific sugar ABC transporter gene was required to invade a model gut consortium, highlighting its importance in microbial competition. Together, these findings establish sugar ABC transporters as genomic predictors of microbial community dynamics in response to dietary sugars.