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Updated: Jul 1, 2025

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Large-scale causal analysis of gut microbiota and six common complications of diabetes: a mendelian randomization

Jiachen Wang1, Menghao Teng2, Ruoyang Feng1

  • 1Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, 710054, Xi'an, Shaanxi, China.

Diabetology & Metabolic Syndrome
|March 14, 2024
PubMed
Abstract

Insights

The gut microbiota (GM) is linked to diabetic complications like hypoglycemia and nephropathy. Specific bacterial classes, Bacteroidia and Verrucomicrobiae, show causal associations, offering new insights into diabetes management.

Area of Science:

  • Microbiome research
  • Metabolic disease research
  • Genetics

Background:

  • Diabetes mellitus is a complex metabolic disorder associated with numerous complications.
  • The gut microbiota (GM) plays a crucial role in host metabolism and immune function.
  • Understanding the interplay between GM and diabetic complications is vital for therapeutic advancements.

Purpose of the Study:

  • To investigate the causal associations between gut microbiota composition and six major diabetic complications.
  • To explore potential microbiome-mediated mechanisms underlying diabetic complications.

Main Methods:

  • Utilized two-sample Mendelian randomization (TSMR) analysis with data from the MiBioGen, Dutch Microbiome Project, and FinnGen consortia.
  • Employed inverse Mendelian randomization (MR) and multivariate MR (MVMR) to assess causality and account for confounding factors.
  • Conducted sensitivity analyses to ensure the robustness and stability of the findings.

Main Results:

  • Identified 61 suggestive causal markers linking gut microbiota and diabetic complications.
  • Found positive associations between the Bacteroidia class/Bacteroidales order and diabetic hypoglycemia.
  • Observed positive associations between the Verrucomicrobiae class/Verrucomicrobiales order and diabetic nephropathy.

Conclusions:

  • Established extensive causal relationships between specific gut microbiota taxa and diabetic complications.
  • These findings suggest novel microbiome-targeted therapeutic strategies for managing diabetes and its sequelae.
  • Highlights the potential of the gut microbiome as a key player in the pathogenesis of diabetic complications.
Keywords:
Complications of diabetesGenome-wise association studiesGut microbiotaMendelian randomization studySingle-nucleotide polymorphism

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