Compositional and genetic alterations in Graves’ disease gut microbiome reveal specific diagnostic biomarkers
Qiyun Zhu, Qiangchuan Hou, Shi Huang, Qianying Ou, Dongxue Huo, Yoshiki Vázquez‐Baeza, Chaoping Cen, Victor Cantu, Mehrbod Estaki, Haibo Chang, Pedro Belda‐Ferre, Ho‐Cheol Kim, Kaining Chen, Rob Knight, Jiachao Zhang
Abstract
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.