BioMeBar Indian Gut Reference Atlas: A Harmonised Multi-Cohort Healthy Microbiome Baseline and the Indian Gut Health Index

Abstract

Population-scale gut microbiome reference databases exist for Western and East Asian cohorts, yet no harmonised healthy baseline has been available for India's 1.4 billion inhabitants, whose diets span extreme geographic and cultural gradients. Western-derived reference ranges risk systematic misclassification when applied to Indian subjects. We harmonised eight published Indian healthy-gut microbiome cohorts (1,672 samples from 1,456 unique individuals , 20 geographic locations, six zones) onto a common NCBI family-level taxonomy axis. Raw 16S rRNA amplicon data were reprocessed through a uniform QIIME 2 / DADA2 / SILVA 138.1 pipeline where raw sequences were available; author-provided taxonomic tables from MetaPhlAn, HITChip, and RDP-based pipelines were retained and mapped via a four-step resolution cascade (exact match, synonym lookup, genus-to-family fallback, Unassigned). We defined the Indian Gut Health Index (IGHI), a four-component composite score (diversity, taxon balance, core membership, community typicality) calibrated against geography-stratified healthy Indian norms. The unified matrix comprised 380 bacterial families, of which 17 constituted the pan-Indian core ([≥]80% prevalence; Lachnospiraceae 100%, Prevotellaceae 99.5%). PERMANOVA confirmed significant compositional differences across geographies (pseudo-F = 43.4, p = 0.001) and cohorts (pseudo-F = 89.6, p = 0.001). Variance partitioning revealed that geography and cohort effects were deeply confounded (shared variance 30.4%; pure geography 4.1%, pure cohort 4.7%, residual 60.9%). Restricted permutation PERMANOVA confirmed city-level geographic signal after cohort correction (p = 0.001), but zone-level signal did not survive (p = 0.896). Two community types were identified: a Prevotellaceae-dominant type (69%) and an Oscillospiraceae-dominant type (31%), contrasting with the Western three-enterotype model. A Random Forest zone classifier achieved 68.4% balanced accuracy (null 16.6%), with Northeast subjects most distinguishable (F1 = 0.92). IGHI zone means ranged from 67.6 to 72.9 (inter-zone range 5.3 points), confirming effective geographic normalisation. Weight sensitivity analysis showed IGHI rankings were robust to moderate perturbation (Spearman {rho} [≥] 0.88 for five of six alternative schemes). The BioMeBarTM Indian Gut Reference Atlas provides the first pan-Indian harmonised healthy microbiome baseline, and the IGHI offers a population-calibrated scoring framework for gut health assessment in Indian individuals. The atlas, scoring model, and analysis code are openly available at https://github.com/TusharParihar128/BioMeBar_Indian_Healthy_Cohorts_datasets.