The coexistence of heart failure (HF) and renal insufficiency, termed cardiorenal syndrome (CRS), significantly increases mortality in HF patients. Although gut microbiota-host metabolic interactions contribute to the pathology of both conditions, their regulatory mechanisms in CRS remain unclear. This cross-sectional study enrolled 451 subjects from two medical institutions across different regions of China, comprising 155 patients with CRS, 225 with HF alone, and 71 controls. Using integrated metabolomics and 16S rRNA sequencing, we compared 801 serum metabolites, 36, 956 microbial amplicon sequence variants, and 14 clinical parameters across the three groups. Additionally, associations between serum metabolites, gut microbiota, and clinical parameters in the HF and CRS groups were analyzed. CRS patients had significantly higher serum uric acid, creatinine, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, along with lower hemoglobin and albumin levels, compared with HF patients (P < 0. 05). Serum metabolomics identified 100 upregulated metabolites in CRS vs. HF (q-value < 0. 1), including endogenous metabolites (3-hydroxybutanoic acid, L-homocitrulline) and gut-derived uremic toxins (3-methyloxindole, p-cresol). Additionally, the CRS group showed significantly reduced gut microbiota α-diversity compared with HF and controls, along with a trend toward reduction in several taxa with key metabolic functions, including Lachnospiraceae, Faecalibacterium, and Faecalibacteriumₚrausnitzii. Moreover, these microbial abundances negatively correlated with endogenous or gut-derived metabolites, while metabolite levels positively correlated with cardiorenal function markers (NT-proBNP, creatinine). This multi-omics study reveals a host-gut microbiota-metabolite association network in CRS, linking aberrant metabolites to microbiota dysbiosis and organ-toxic metabolite accumulation. These findings provide novel insights into CRS pathogenesis and potential targeted therapies. Clinical trial number: ChiCTR2300071422.
Rao et al. (Tue,) studied this question.