Arrhythmic Gut Microbiome Signatures for Risk Profiling of Type-2 Diabetes

Lifestyle, obesity and the gut microbiome are among the most important risk factors for the development of metabolic disorders. We demonstrate in 1,976 subjects of a prospective population cohort (KORA) that specific gut microbiota members show 24-hour oscillations in their relative abundance and identified 13 taxa with disrupted rhythmicity in T2D. Cross-validated prediction models based on this signature classified T2D with an AUC of 73%. BMI as independent factor improved classification of T2D. The validity of this arrhythmic signature was confirmed in 699 KORA subjects five years after initial sampling, being most effective in combination with BMI and microbiota (AUC=78%). Shotgun metagenomic analysis functionally linked 26 metabolic pathways to the diurnal oscillation of gut bacteria. In summary, we determined a cohort-specific risk pattern of arrhythmic taxa which significantly contributes to the classification and prediction of T2D, suggesting a functional link between circadian rhythmicity and the gut microbiome in metabolic diseases.