Indigenous Yanomami gut microbiota protects against diet-induced metabolic dysfunction

Industrialization profoundly alters the human gut microbiota, reducing microbial diversity and eliminating taxa prevalent in non-industrialized populations. These microbiota alterations accompanying industrialization might contribute to the increasing prevalence of obesity and other chronic inflammatory diseases, yet direct experimental evidence remains lacking. We compared the gut microbiota of Indigenous Brazilian Yanomami and urban Belgian donors and transplanted these into germ-free (GF) mice subjected to high-fat diet (HFD). The Yanomami microbiota exhibited greater richness and distinct composition enriched for VANISH (Volatile and/or Associated Negatively with Industrialized Societies of Humans) taxa. Transplantation of Yanomami microbiota significantly attenuated HFD-induced metabolic dysfunction, reducing weight gain, diabetes incidence, and promoting adipose and hepatic Th2 immunity. Yanomami-derived microbial communities displayed enhanced ecological stability and enrichment for short-chain fatty acid-associated taxa and metabolic functions post-HFD. Our findings demonstrate that the microbiota from low-urbanization populations confer protection against diet-induced metabolic disease, highlighting ecological resilience and specific microbial functions as potential targets for microbiota-inspired therapeutics.