Distinct trajectories of urbanization shape the human gut microbiome across South Asia.

Human gut microbiomes respond to lifestyle transitions, yet the extent to which these responses are conserved across spatio-cultural contexts remains undercharacterized. We present the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase nonpersistence. Concurrently, we identify significant associations of urbanization markers with increased abundance of disease-linked taxa, especially Megamonas-correlated with increased blood glucose and lower gut microbiome diversity-which is enriched in SAMBAR over comparative global regions. Overall, microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography, and underscoring the need for community-specific investigations of health impacts.