The gut microbiome composition is altered in long-standing type 1 diabetes and associates with glycemic control and disease-related complications

Objective: People with type 1 diabetes are at risk of developing micro- and macrovascular complications. Little is known about the gut microbiome in long-standing type 1 diabetes. We explored differences in the gut microbiome of participants with type 1 diabetes compared to healthy controls and associated the gut microbiome with diabetes-related complications.

Research Design and Methods: Microbiome data of 238 participants with type 1 diabetes with an average disease duration of 28 (±15) years were compared to 2937 age-, sex- and BMI-matched individuals. Clinical characteristics and fecal samples were collected and metagenomic shotgun sequencing was performed. Microbial taxonomy was associated with type 1 diabetes–related characteristics and vascular complications.

Results: No significant difference in the α-diversity of the gut microbiome was found between participants with type 1 diabetes and healthy controls. However, 43 bacterial taxa were significantly depleted in type 1 diabetes, while 37 bacterial taxa were significantly enriched. HbA1c and disease duration explained a significant part of variation in the gut microbiome (R2>0.008, FDR<0.05), and HbA1c was significantly associated with the abundance of several microbial species. Additionally, both micro- and macrovascular complications explained a significant part of variation in the gut microbiome (R2>0.0075, FDR<0.05). Nephropathy was strongly associated with several microbial species. Macrovascular complications displayed similar associations to nephropathy.

Conclusion: Our data show that the gut microbiome is altered in people with (long-standing) type 1 diabetes and is associated to glycemic control and diabetes-related complications. Due to the cross-sectional design, the causality of these relationships remains to be determined.