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

Abstract

Background This study aimed to reveal the association between the gut microbiota (GM) and six diabetic complications: diabetic hypoglycemia; ketoacidosis; nephropathy; neuropathy; retinopathy; and Charcot’s foot. Methods GM data were obtained from the MiBioGen consortium and Dutch Microbiome Project while data on the six diabetic complications were obtained from the FinnGen consortium. Two-sample Mendelian randomization (TSMR) was performed to explore the association between GM and the common diabetic complications. Inverse MR analysis was conducted to examine the effect of diabetic complications on the identified GM. Sensitivity tests were conducted to validate the stability of the results. Finally, multivariate MR (MVMR) was performed to determine whether GM had a direct influence on the diabetic complications. Results After multiple corrections, the inverse variance weighted (IVW) results predicted 61 suggestive markers between GM and six diabetic complications. In particular, the IVW results revealed that the Bacteroidia class and Bacteroidales order were positively associated with diabetic hypoglycemia while the Verrucomicrobiae class and Verrucomicrobiales order were positively associated with diabetic nephropathy. Based on the replication analysis, these results were identified to be stable. MVMR showed that the results remained stable after accounting for traditional risk factors. Conclusion Extensive causal associations were found between GM and diabetic complications, which may provide new insights into the mechanisms of microbiome-mediated complications of diabetes.

Association of Circulating Markers of Microbial Translocation and Hepatic Inflammation with Liver Injury in Patients with Type 2 Diabetes

“…Intestinal barrier dysfunction and ensuing gut microbial translocation and systemic inflammation are essential components of the pathogenic changes in the “gut–liver axis” leading to liver disease. In this regard, alterations in gut microbiota have been documented in subjects with T2DM [ 50 , 51 , 52 , 53 ]; however, the understanding of the relevance of gut-derived events leading to hepatic inflammation and injury as a diabetic complication remains to be fully clarified. Hence, in the present pilot study, we examined the association of gut permeability and microbial translocation markers with markers of systemic/hepatic inflammation and liver injury.…”

The causal relationship between gut microbiota and diabetic neuropathy: a bi-directional two-sample Mendelian randomization study

“…In recent times, there has been significant focus on the gut microbiota in metabolic illnesses, specifically type 2 diabetes. This topic has been extensively explored in scientific literature ( 28 ). In addition, previous studies have used MR analysis to elucidate potential causal relationship between various biomarkers from different sources and the risk of various diseases ( 29 – 31 ).…”