Work

Impact of Dapagliflozin on Gut Microbiota and Plasma Metabolomic Profiles in Patients With Heart Failure

Year: 2025

Type: article

Abstract: Background: Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Although dapagliflozin, a selective sodium–glucose cotransporter 2 (SGLT2) inhibitor, has demonstrated significant cardiovascular benefits in large clinical trials, the underlying mechanisms beyond glucose lowering remain incompletely understood. Increasing evidence suggests that gut microbiota and its metabolites may contribute to HF progression through gut–heart axis interactions. Methods: In this study, a total of 135 individuals with HF were recruited, comprising 84 patients treated with dapagliflozin (Y group) and 51 receiving conventional therapy (N group). Gut microbial communities were characterized through 16S rRNA gene sequencing to evaluate compositional structure, diversity metrics, and taxa differences between groups. Untargeted metabolomic profiling of plasma samples was conducted to identify significantly altered metabolites and enriched metabolic pathways. Furthermore, the interrelationships between gut bacterial taxa and circulating metabolites were systematically explored to delineate potential microbiome–metabolome interactions. Results: Dapagliflozin treatment significantly altered gut microbial composition (p < 0.05, permutational multivariate analysis of variance [PERMANOVA]), characterized by increased Prevotella, Akkermansia, Collinsella, and Fusobacterium, and reduced Bacteroides, Parabacteroides, Subdoligranulum, and Bifidobacterium in the dapagliflozin group, whereas control-enriched taxa included Lachnoclostridium and the Ruminococcus gauvreauii group. Fourteen plasma metabolites were differentially abundant between groups, including higher levels of O-phospho-L-threonine and epiandrosterone in the dapagliflozin group, while salicyluric acid and L- (+)-rhamnose were enriched in the control group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated alterations in amino acid and one-carbon metabolism, as well as carbohydrate and steroid-related pathways. Correlation analysis revealed that Collinsella was positively associated with fludarabine phosphate (p < 0.05), whereas Akkermansia and Paraprevotella showed negative correlations with maslinic acid and phospho-L-valine, respectively (p < 0.01 to p < 0.001). Conclusion: Dapagliflozin modulates gut microbiota composition and circulating metabolic signatures in HF patients, supporting a potential gut–heart axis mechanism contributing to its cardioprotective effects.

Source: Frontiers in Bioscience-Landmark

DOI: 10.31083/fbl46142