Causal relationships between gut microbiota, gut metabolites, and diabetic neuropathy: A mendelian randomization study

Background: Previous studies have shown a strong correlation between gut microbiota and diabetes and its associated complications. We aimed to evaluate the causal relationships between the gut microbiota, gut metabolites, and diabetic neuropathy. Methods: Summary statistics of 211 gut microbiota and 12 gut -related metabolites ( b -hydroxybutyric acid, betaine, trimethylamine-N-oxide, carnitine, choline, glutamate, kynurenine, phenylalanine, propionic acid, serotonin, tryptophan, and tyrosine) were obtained from previous genome-wide association studies (GWAS). A two -sample Mendelian randomization (MR) design was used to estimate the effects of gut microbiota and gut metabolites on the risk of diabetic neuropathy based on FinnGen GWAS. Results: Higher levels of Acidaminococcaceae (OR = 0.62; 95%CI = 0.46 to 0.84; P = 0.002), Peptococcaceae (OR = 0.70; 95%CI = 0.54 to 0.90; P = 0.006), and Eubacterium coprostanoligenes group (OR = 0.68; 95%CI = 0.50 to 0.93; P = 0.016) are genetically determined to provide protection against diabetic neuropathy. Conversely, the presence of Alistipes (OR = 1.65; 95%CI = 1.18 to 2.31; P = 0.003), Christensenellaceae R7 group (OR = 1.52; 95%CI = 1.03 to 2.23; P = 0.033), Eggerthella (OR = 1.28; 95%CI = 1.05 to 1.55; P = 0.014), Ruminococcaceae UCG013 (OR = 1.35; 95%CI = 1.01 to 1.82; P = 0.046), and Firmicutes (OR = 1.42; 95%CI = 1.05 to 1.93; P = 0.023) increases the risk of diabetic neuropathy. Moreover, a correlation has been identi fied between diabetic neuropathy and two gut metabolites: betaine (OR = 0.95; 95%CI = 0.90 to 1.00; P = 0.033) and tyrosine (OR = 1.03; 95%CI = 1.01 to 1.06; P = 0.019). Sensitivity analysis indicated robust results with no sign of heterogeneity or pleiotropy. Conclusion: The present study elucidated the impact of speci fic gut microbiota and gut metabolites on the susceptibility to diabetic neuropathy. Interventions targeting the improvement of the gut microbiota diversity and composition hold considerable promise as a potential strategy. (c) 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.