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 for 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 with healthy control subjects 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 with 2,937 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 alpha-diversity of the gut microbiome was found between participants with type 1 diabetes and healthy control subjects. However, 43 bacterial taxa were significantly depleted in type 1 diabetes, while 37 bacterial taxa were significantly enriched. HbA(1c) and disease duration explained a significant part of the variation in the gut microbiome (R-2 > 0.008, false discovery rate [FDR] <0.05), and HbA(1c), was significantly associated with the abundance of several microbial species. Additionally, both micro- and macrovascular complications explained a significant part of the variation in the gut microbiome (R-2 > 0.0075, FDR < 0.05). Nephropathy was strongly associated with several microbial species. Macrovascular complications displayed similar associations with nephropathy. CONCLUSIONS Our data show that the gut microbiome is altered in people with (long-standing) type 1 diabetes and is associated with glycemic control and diabetes-related complications. As a result of the cross-sectional design, the causality of these relationships remains to be determined.