Dissecting causal relationships between gut microbiota, inflammatory factors, and acute kidney injury: A Mendelian randomization study.

Background: Acute kidney injury (AKI) is common in critically ill patients in the medical intensive care unit (ICU), and it is associated with increased morbidity and mortality. Recent studies suggest a significant link between AKI and disturbances in the gut microbiota (GM).

Materials and methods: We used summary genome-wide association studies (GWAS) data from MiBioGen for GM and AKI data from the FinnGen cohort. Causal relationships were primarily assessed using the inverse variance weighted (IVW) method, with MR-PRESSO and MR-Egger tests to address potential horizontal pleiotropy. Heterogeneity was evaluated using Cochran's Q and I² values.

Results: The IVW method revealed a causal association between 14 gut microbial taxa and AKI. The Phylum Firmicutes (id. 1672), Order Pasteurellales (id. 3688), Genus unknowngenus (id. 2071), Genus RuminococcaceaeUCG010 (id. 11367), Genus RuminococcaceaeUCG005 (id. 11363), Genus Haemophilus (id. 3698), Genus Flavonifractor (id. 2059), Genus ErysipelotrichaceaeUCG003 (id. 11384), Genus Dialister (id. 2183), Genus Coprococcus2 (id. 11302), and Family Pasteurellaceae (id. 3689) were negatively associated with AKI risk. Conversely, Genus Victivallis (id. 2256), Genus RuminococcaceaeUCG013 (id. 11370), and Genus Erysipelatoclostridium (id. 11381) were positively associated with AKI risk. Additionally, hepatocyte growth factor (HGF), interleukin-10 (IL-10), fibroblast growth factor-23 (FGF-23), and tumor necrosis factor alpha (TNF-α) were potentially causative in AKI onset.

Conclusion: This study emphasizes the significant role of gut microbiota interactions with inflammatory factors in AKI pathogenesis. The identified risk factors underscore their essential role in both the onset and progression of AKI.