Identification of gut microbiome features associated with host metabolic health in a large population-based cohort

The complex relationship between the gut microbiome and host metabolic health has been an emerging research area. Several recent studies have highlighted the potential effects of the microbiome's diversity, composition and metabolic production capabilities on Body Mass Index (BMI), liver health, glucose homeostasis and Type-2 Diabetes (T2D). The majority of these studies were constrained by relatively small cohorts, mostly focusing on individuals with metabolic disorders, limiting a comprehensive understanding of the microbiome's role in metabolic health. Leveraging a large-scale, comprehensive cohort of nearly 9000 individuals, measured using Continuous Glucose Monitoring (CGM), Dual-energy X-ray absorptiometry (DXA) scan and liver Ultrasound (US) we examined the functional profile of the gut microbiome, and its relation to 38 metabolic health measures. We identified 145 unique bacterial pathways significantly correlated with metabolic health measures, with 86.9% of these showing significant associations with more than one metabolic health measure. Furthermore, 87,678 unique bacterial gene families were found to be significantly associated with at least one metabolic health measure. Notably, "key" bacterial pathways such as purine ribonucleosides degradation and anaerobic energy metabolism demonstrated multiple robust associations across various metabolic health measures, highlighting their potential roles in regulating metabolic processes. Our results remained largely unchanged after adjustments for nutritional habits and for BMI they were replicated in a geographically independent cohort. These insights pave the way for future research and potentially the development of microbiome-targeted interventions to enhance metabolic health.