Gut microbial diversity and candidate keystone taxa in Indian tribes: Insights across lifestyle-ecological continuum and health associations.

Despite the critical role of the gut microbiome in host physiology and health, it remains poorly characterized in Indigenous populations undergoing rapid acculturation. This study presents high-resolution, whole-genome metagenomic profiling of gut microbiota from five Particularly Vulnerable Tribal Groups (PVTGs) of Southern India, Irula, Jenu Kuruba, Kurumba, Chenchu, and Konda Savara, spanning distinct ecological zones and cultural transitions. Using an ecology-lifestyle continuum framework, we investigated taxonomic and functional diversity with a focus on identifying computationally inferred candidate keystone taxa, defined by their association with variation in community ordination structure. A leave-one-taxon-out ordination framework identified 121 candidate keystone taxa, many of which were population-specific and have not been widely reported. Functional analyses revealed a conserved core of metabolic pathways, including glycolysis and folate biosynthesis, alongside group-specific enrichment in xenobiotic degradation, amino acid biosynthesis, mucin metabolism, and lipid processing, associated with differences in dietary and environmental exposures across populations. Large-scale disease-association mapping (n = 5,625) linked 50 candidate keystone taxa to 14 conditions, with 44 associated with health and 6 with disease. While