Synergy between Enterobacteriaceae and diet mediates competition between dominant Bacteroidales in the human gut

Abstract Healthy human gut microbiota is dominated by Bacteroidaceae in industrialized populations and by Prevotellaceae in those with traditional lifestyles, but diet alone is insufficient to explain this dominance of different Bacteroidota. Here we screened 94 dietary components in synthetic gut communities and find that these two bacterial families compete for overlapping nutritional niches. Segatella copri , a key member of Prevotellaceae-rich communities, outcompeted Bacteroidaceae when preferred polysaccharides such as arabinan were available, but this advantage depended on community composition, particularly the presence of Enterobacteriaceae. Metatranscriptomics and targeted metabolomics further revealed that Enterobacteriaceae synergized with dietary components to promote Segatella dominance in human and mouse gut communities. These interactions were validated by using multiple E. coli and Segatella isolates. Analyses of global metagenomes also showed a positive correlation between Segatella -rich non-industrialized microbiomes and Enterobacteriaceae abundance. Our results establish an ecosystem-level dynamic interplay between dietary components and key gut commensals that favour the dominance of Prevotellaceae.