Abstract
This study investigates the roles of gut microbiome and secondary bile acid dysfunctions in type 1 diabetes (T1D) and explores targeted interventions to address them. It finds that T1D is associated with reduced gut microbial diversity and imbalance favoring harmful bacteria over beneficial ones. Additionally, patients with T1D exhibited impaired secondary bile acid metabolism. Interventions aimed at modulating the gut microbiome and metabolites are safe and improve glycemic control, reduce daily insulin dose, and reduce inflammation. These interventions reshape the gut microbiome toward a healthier state and enhance secondary bile acid production. Responders to the interventions show increased levels of beneficial bacteria and secondary bile acids, along with improved C-peptide responses. Overall, these findings suggest that targeted modulation of the gut microbiome and secondary bile acid metabolism could be a promising therapeutic approach for T1D management. The trial is registered at Chinese Clinical Trial Registry (ChiCTR-ONN-17011279).