Metabolomic interplay between gut microbiome and plasma metabolome in cardiac surgery-associated acute kidney injury

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a prevalent complication of cardiac surgery, which may be associated with a great risk of developing chronic kidney disease and mortality. Comprehensively understanding the effects of host gut microbiota metabolism on the pathogenesis of CSA-AKI will be helpful for the diagnosis and treatment of the disease. This study aimed to investigate the possible links between gut microbiota metabolism and CSA-AKI.

Methods: A prospective cohort of patients who underwent cardiac surgery were continuously recruited, and they were further divided into the CSA-AKI group and Non-AKI group based on the clinical outcomes. Their faecal and plasma samples were collected before the surgery and were separately analysed by non-targeted and targeted metabolomics. The differential metabolites related to CSA-AKI were screened out using multivariate and univariate statistical methods, and altered metabolic pathways were determined by examining the Kyoto Encyclopedia of Genes and Genomes database.

Results: Nearly 1000 faecal metabolites were detected through high-resolution mass spectrometry (MS) and bioinformatics at annotation levels 1–3, and 49 differential metabolites (levels 1–2) may perform essential biological functions and provide potential diagnostic indicators. Compared with the Non-AKI group, the patients in the CSA-AKI group displayed dramatic changes in gut microbiota metabolism, including amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and ABC transporters. Meanwhile, a total of 188 plasma metabolites were identified and quantified by tandem MS, and 34 differential plasma metabolites were screened out between the two groups using univariate statistical analysis. These differential plasma metabolites were primarily enriched in the following metabolic pathways: sulphur metabolism, amino acid biosynthesis, tryptophan metabolism, and ABC transporters. Furthermore, the content of indole metabolites in the faecal and plasma samples of the CSA-AKI group was higher than that of the Non-AKI group.

Conclusions: Patients with CSA-AKI may have dysbiosis of their intestinal microbiota and metabolic abnormalities in their gut system before cardiac surgery. Thus, some metabolites and related metabolic pathways may be potential biomarkers and new therapeutic targets for the disease. The application of MS-based metabolomic interplay can provide data on faecal and plasma metabolite markers and valuable resources for the pathogenic mechanism of the gut microbiota on CSA-AKI.