Association of gut microbiota with acute kidney injury: a two-sample Mendelian randomisation and case-control study.

Abstract

Epidemiologic studies have implicated the gut microbiota in acute kidney injury (AKI), but the causal relationship is unclear. Using Mendelian randomisation, we explored the causal role of gut microbiota in the development of acute kidney injury after excluding confounding and reverse causality. Mendel randomised (MR) study was conducted using data from intestinal microbiota and genome-wide association studies (GWAS) disease of acute kidney injury and the sequencing data of case-control study confirmed this finding. The summary statistics of intestinal microbiota (n= 13,266) conducted by MiBioGen Alliance was taken as the exposure, while the statistics of acute kidney injury obtained from FinnGen Alliance data (2,383 cases and 212,841 controls) were taken as the results. A total of 42 patients were included in this case-control study. Evidence for the protective causal associations of the genus Flavonifractor id.2059 with AKI was found in inverse variance weighting (odds ratio= 0.48 [95% confidence interval, 0.32-0.72]; P = 0.0003). Additionally, a case-control study showed that the relative abundance of the genus Flavonifractor id.2059 ( P = 0.0169) in septic non-AKI patients was higher than that in septic AKI patients. Compared with S-AKI patients who died within 28 days, the relative abundance of the genus Flavonifractor id.2059 in surviving patients was higher ( P = 0.0281). Phylogenetic analysis showed that OTU68 and HQ455040.1334-739 (genus Flavonifractor, Genetic similarity: 100%), as well as OTU2271 and LT598575.1365-770 (genus Pseudoflavonifractor, Genetic similarity: 100%), have closest genetic ties. Correlation analysis showed that the genus Flavonifractor id.2059 was related to the creatinine value (Spearman correlation: -0.379, P = 0.013). The present study demonstrates that the genus Flavonifractor id.2059 is associated with a reduced risk of AKI, revealing potential implications for the prevention and treatment of acute kidney injury.