Co-Enrichment of Desulfovibrio and Erysipelotrichaceae and Dysregulation of Multiple Amino Acid Pathways in HFpEF: Insights into TXG-Associated Metabolic Changes.

Gut enrichment of Desulfovibrio and Erysipelotrichaceae may be associated with systemic amino acid metabolic dysfunction, myocardial injury, and heart failure with preserved ejection fraction (HFpEF). These taxa appear to influence host amino acid metabolism through distinct processes, but the functional implications of their co-enrichment in HFpEF remain unclear. Total xanthones from Gentianella acuta (TXG) have documented cardioprotective effects, although their effects on gut microbiota and systemic metabolism remain unexplored. We established a mouse model of HFpEF using a high-fat diet (HFD) combined with Nω-nitro-L-arginine methyl ester (L-NAME). We integrated 16S rRNA sequencing, fecal metagenomics, and targeted serum amino acid metabolomics to examine microbe-metabolite associations, with echocardiography and histopathology providing complementary phenotypic evidence. Microbial and metabolomic analyses revealed pronounced enrichment of Desulfovibrio and Erysipelotrichaceae (particularly Dubosiella), accompanied by elevated serum isoleucine, tryptophan, and homocysteine levels. TXG treatment was associated with lower abundance of both taxa, altered serum amino acid profiles, preserved colonic barrier integrity, and reduced myocardial inflammation and fibrosis. These changes coincided with improved diastolic function. Together, these findings associate co-enrichment of the two taxa with dysregulation of multiple amino acid pathways in HFpEF. TXG treatment was accompanied by attenuated cardiac and metabolic injury as well as shifts in gut-microbiota profiles, with these correlative observations motivating further investigation of Gentianella acuta for metabolic heart failure.