The Gut Microbiome Composition Is Altered in Long-standing Type 1 Diabetes and Associates With Glycemic Control and Disease-Related Complications

Diabetes Care. 2022 Sep 1;45(9):2084-2094. doi: 10.2337/dc21-2225.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1* / complications
  • Gastrointestinal Microbiome* / genetics
  • Glycated Hemoglobin
  • Glycemic Control
  • Humans

Substances

  • Glycated Hemoglobin A

Associated data

  • figshare/10.2337/figshare.20032256