The study on the identification of cross-boundary microbiome enterotypes between high-altitude and coastal populations and their predictive value

Abstract Objective To investigate the differences in gut microbiome composition among multi-center populations from coastal and high-altitude regions of China and their association with colorectal adenoma (CRA). Methods and analysis Metagenomic sequencing was performed on stool samples collected from 295 participants. Diversity, principal component, and linear discriminant analyses were conducted to assess microbial composition and functional differences related to geography and disease status. Results In high-altitude populations, bacterial enterotypes were predominantly Prevotella, fungal enterotypes Saccharomyces, and archaeal enterotypes Methanobrevibacter, differing from those in coastal populations. Combining bacterial, fungal, and archaeal features improved classification accuracy between high-altitude and coastal populations (AUC = 0.84) and between high-altitude and coastal adenoma patients (AUC = 0.85). Specific enterotypes were observed to correlate significantly with metabolic pathways in high-altitude populations. Conclusion Significant differences in gut microbiome enterotypes exist across geographic populations, with specific enterotypes in high-altitude populations potentially associated with a lower prevalence of CRA. These findings provide new insights into the gut microbiome–geography relationship and support microbiome-based diagnostic and therapeutic strategies.