Comparisons among Yanomami populations reveal transitional gut microbiome configurations under urban influence

Urbanization influences gut microbiome composition and function, yet comparisons between contrasting lifestyles offer limited insight into which microbial features are most sensitive to increasing urbanization. We analyzed gut shotgun metagenomes from Yanomami participants, an Indigenous Amazonian people who maintain traditional livelihoods, across three geographically distinct populations with varying degrees of urban influence, as well as an urban Belgian cohort. Belgian and Yanomami microbiomes differed markedly in taxonomic composition and functional potential. The comparison between Bicho-Açu, the most urban-influenced Yanomami population, and Xamakorona, the least urban-exposed, revealed that although Bicho-Açu presented a broadly Yanomami-associated microbiome, it exhibited selected urban-associated features, including greater Bacteroides abundance and a higher relative abundance of genes involved in glycosaminoglycan degradation and secondary bile acid biosynthesis pathways. Furthermore, genus-level co-occurrence network connectivity showed an orderly shift across populations, declining progressively with increasing urban influence. Carbohydrate-active enzyme profiles further showed stronger non-starch-polysaccharide-associated signals in Belgium and resistant-starch-associated features in Xamakorona, suggesting distinct carbohydrate-processing strategies. Our findings support a model in which urbanization reshapes microbial composition, their ecological interactions, and metabolic capacity, with transitional configurations emerging through selective shifts across these dimensions.