The Gut Microbiome Composition Is Altered in Long-standing Type 1 Diabetes and Associates With Glycemic Control and Disease-Related Complications
Julia I. P. van Heck, Ranko Gaćeša, Rinke Stienstra, Jingyuan Fu, Alexandra Zhernakova, Hermie J. M. Harmsen, Rinse K. Weersma, Leo A. B. Joosten, Cees J. Tack
Abstract
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 α-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. HbA1c and disease duration explained a significant part of the variation in the gut microbiome (R2 > 0.008, false discovery rate [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 the variation in the gut microbiome (R2 > 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.