Compositional and genetic alterations in Graves’ disease gut microbiome reveal specific diagnostic biomarkers

Graves’ Disease is the most common organ-specific autoimmune disease and has been linked in small pilot studies to taxonomic markers within the gut microbiome. Important limitations of this work include small sample sizes and low-resolution taxonomic markers. Accordingly, we studied 162 gut microbiomes of mild and severe Graves’ disease (GD) patients and healthy controls. Taxonomic and functional analyses based on metagenome-assembled genomes (MAGs) and MAG-annotated genes, together with predicted metabolic functions and metabolite profiles, revealed a well-defined network of MAGs, genes and clinical indexes separating healthy from GD subjects. A supervised classification model identified a combination of biomarkers including microbial species, MAGs, genes and SNPs, with predictive power superior to models from any single biomarker type (AUC = 0.98). Global, cross-disease multi-cohort analysis of gut microbiomes revealed high specificity of these GD biomarkers, notably discriminating against Parkinson’s Disease, and suggesting that non-invasive stool-based diagnostics will be useful for these diseases.