Urbanization, Ethnicity and Diet Shape Gut Microbial Structural Variations

Structural variations (SVs) represent an important dimension of bacterial genomic diversity, yet their variation across diverse human populations remains poorly understood. Here, we profiled gut microbial SVs using previously published metagenomic data from 860 individuals representing 6 ethnic groups in Yunnan, China. Host and environmental metadata collectively explained approximately one-third of SV variation, with urbanization, diet, and ethnicity showing the largest marginal contributions. However, overall urban–rural residency differences were small after multivariable adjustment, whereas numerous residency-associated SVs emerged within individual ethnic groups with minimal overlap across groups. In contrast, ethnicity-associated SV differentiation persisted in an independent rural cohort comprising the same 6 ethnic groups and was accompanied by broader strain-level genomic differentiation. Dietary differences may partly contribute to these population-specific associations, as supported by significant mediation pathways linking ethnicity, diet, and SVs. Comparisons with international cohorts further placed the within-Yunnan heterogeneity in a broader geographic and lifestyle context. Together, these findings identify ethnic background as a major population-level context for gut microbial structural variation, within which urbanization- and diet-associated differences are further differentiated.