Causal relationship of gut microbiota with diabetic nephropathy: a Mendelian randomization analysis

Abstract

BackgroundPatients with DN (diabetic nephropathy) show remarkable variations in their gut microbiota composition. However, to date, no study has shown whether a causal relationship exists between gut microbiota composition and DN.MethodsHere, we performed a two-sample Mendelian randomization (MR) investigation for identifying causal associations of gut microbiota with DN. Gut microbiota genetic data were gathered from the recent genome-wide association study pooled data of the MiBioGen consortium, which included 24 cohorts and 18,340 individuals.ResultsIVW(Inverse variance weighting) revealed that Verrucomicrobia [odds ratio (OR) = 1.390; 95% confidence interval (CI) = 1.10–1.75; p = 0.005], Peptostreptococcaceae (OR = 1.284; 95% CI = 1.03–1.59; p = 0.012), Verrucomicrobiaceae (OR = 1.390; 95% CI = 1.10–1.75; p = 0.005), Akkermansia (OR = 1.390; 95% CI = 1.10–1.75; p = 0.005), Butyricimonas (OR = 1.261; 95% CI = 1.02–1.55; p = 0.031), Catenibacterium (OR = 1.278; 95% CI = 1.02–1.59; p = 0.030).ConclusionTwo-sample MR analysis identified 12 microbial taxa in gut microbiota (one of which is yet to be officially named) that showed significant causal associations with DN; 8 of these taxa significantly increased the risk of DN, while the remaining 4 taxa (including the one without an official name) reduced the risk of DN. The precise mechanisms influencing the interactions of gut microbiota with DN occurrence remain unclear; hence, additional investigations should be conducted to clarify these mechanisms.