Landscape of human gut antibiotic resistome and progression of diabetes

Objective: To investigate the association between human gut antibiotic resistome and the progression of type 2 diabetes (T2D) in a large cohort study. Design: The present study included 1210 participants from the Guangzhou Nutrition and Health Study. We depicted the landscape of human gut antibiotic resistome with shotgun metagenomic data and examined its association with T2D and cardiometabolic traits. The co-occurrence network analysis was used to explore the associations between T2D-related ARGs and gut microbial species. We also examined the associations between gut antibiotic resistome features and fecal metabolome. Results: There was a significant overall shift in gut antibiotic resistome structure among healthy, prediabetes and T2D groups (p = 0.004). We found that larger ARG diversity was associated with a higher risk of T2D (all p < 0.05). Based on the association found between resistomes and T2D, we developed diabetes ARG score and demonstrated its creative use as a new predictor for T2D progression manifested by the change of insulin resistance. Further network analysis showed the co-occurrence association between T2D-related ARGs and gut microbial species, which indicated the potential bacterial hosts of these ARG biomarkers. Resistome-metabolome co-analysis suggests a potential link of ARGs with fecal metabolites, which may reflect the host-microbial metabolic adaptation. Conclusion: Our data depict the landscape of gut antibiotic resistome diversity and composition and uncover a close relationship between human gut antibiotic resistome and T2D progression.