TaxoMFM: A Taxonomy-Aware Foundation Model for the Human Gut Microbiome

Abstract

Existing gut microbiome foundation models typically use flat taxon representations, limiting their ability to exploit known taxonomic hierarchies. We introduce TaxoMFM, a microbiome foundation model that integrates taxonomic structure into self-supervised learning. TaxoMFM jointly learns abundance patterns across taxonomic ranks and relative proportions within groups through taxonomy-aware encoding and hierarchical compositional reconstruction. We further construct TaxoGut-HPP, comprising 100,806 gut microbiome profiles from 231 source cohorts and covering 40 classification and 8 regression tasks. TaxoMFM achieves competitive performance across disease, gut health, host trait, and liver ultrasound phenotype prediction. In cross-cohort zero-shot transfer, where target cohorts are excluded from both pretraining and downstream adaptation, TaxoMFM achieves AUROCs of 0.838, 0.736, and 0.722 for colorectal cancer, type 2 diabetes, and inflammatory bowel disease, respectively. Further analyses show that TaxoMFM recovers community changes across taxonomic scales, while preserving community information and producing consistent representations under database updates and species-vocabulary shifts. Our code is available at https://anonymous.4open.science/r/TaxoMFM-F16D/.