Association between gut microbiota and diabetic microvascular complications: a two-sample Mendelian randomization...

Area of Science:

• Microbiome research
• Genetics
• Metabolic diseases

Background:

• Gut microbiota (GM) homeostasis is crucial for overall health and disease prevention.
• Diabetic microvascular complications, including diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP), impose significant burdens.
• Targeting GM alterations presents a potential strategy to mitigate these complications.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and diabetic microvascular complications (DKD, DR, DNP) using a two-sample Mendelian randomization approach.
• To identify specific gut microbial traits causally associated with the risk of developing DKD, DR, and DNP.

Main Methods:

• Utilized genome-wide association study (GWAS) summary statistics for GM and diabetic microvascular complications.
• Performed forward Mendelian randomization (MR) analysis with sensitivity tests (heterogeneity, pleiotropy, leave-one-out, Steiger, reverse MR) to ensure robust causal inference.
• Selected 2,092 single-nucleotide polymorphisms related to 196 bacterial traits as instrumental variables.

Main Results:

• Identified 28 genetically predicted abundances of specific GM causally associated with DKD, DR, and DNP.
• Found causal links between 23 gut microbial traits and the occurrence of these diabetic complications, with odds ratios generally ranging from 0.9 to 1.1.
• Sensitivity analyses confirmed low heterogeneity, low pleiotropy, and high reliability of the causal estimates.

Conclusions:

• Gut microbiota represents a potential therapeutic target for preventing and delaying the progression of diabetic microvascular complications.
• Further experimental research is necessary to elucidate the precise mechanisms of GM therapy in managing these conditions.