Shengxian decoction modulates gut microbiota and microbial metabolism in rats with chronic heart failure

Chronic heart failure (CHF) is a complex syndrome characterized by high morbidity and mortality, imposing a substantial global health burden. Shengxian Decoction (SXT) is a Traditional Chinese Medicine formulation that has demonstrated efficacy in treating CHF. However, its mechanism for modulating the gut microbiota in transverse aortic constriction (TAC)-induced CHF rats remains unclear.

This study identified components of SXT using liquid chromatography-mass spectrometry (LC-MS). A CHF model was established in rats via TAC surgery. Cardiac function was assessed by echocardiography, and hematological parameters were subsequently analyzed. Myocardial and colonic histopathology were examined by H&E staining, and myocardial fibrosis was evaluated using Masson's trichrome staining. Intestinal barrier function was assessed using immunohistochemistry (IHC), Western blotting, and RT-qPCR analyses. Fecal 16S rRNA gene sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolomics were performed across groups to characterize the gut microbiota and its associated metabolites. Furthermore, MetOrigin and Spearman's correlation analysis were employed to characterize the associations between gut microbiota and metabolites.

In total, 147 components were identified in SXT. SXT treatment improved cardiac function in CHF rats and reduced serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Furthermore, SXT ameliorated pathological alterations in myocardial and colonic tissues and restored the expression of occludin and ZO-1 in colonic tissue. Among them, the high-dose SXT group showed the most prominent therapeutic effect. 16S rRNA sequencing revealed that SXT ameliorated gut microbiota dysbiosis, identifying 17 differentially abundant bacterial genera. Among these, SXT increased the abundance of genera capable of producing short-chain fatty acids. Fecal metabolomic analysis identified 27 differential metabolites. After SXT treatment, levels of glycocholic acid, cholic acid, chenodeoxycholic acid, and prostaglandin A2 were elevated, whereas palmitic acid and metanephrine were reduced. Metabolite tracing analysis indicated that primary bile acid biosynthesis is a key host-microbe co-metabolic pathway. Spearman correlation analysis revealed significant associations between differential gut bacterial genera and differential metabolites.

This study demonstrates the therapeutic efficacy of SXT in alleviating CHF and its potential to regulate microbial-host co-metabolism. These findings provide new insights into the mechanisms underlying the effects of SXT in CHF.