Effect of Shenqi Buqi Granule on TMAO-related Metabolites in Plasma and Gut Microbiota in Rats with Chronic Heart Failure

MIAO Lan; MENG Shuo; PENG Qing; SUN Mingqian; REN Changying; LIN Li; LIU Jianxun

Abstract：Objective This study aims to investigate the impact of Shenqi Buqi granule (SQBQ) on plasma trimethylamine oxide (TMAO) and its associated metabolites,as well as intestinal flora in rats with chronic heart failure. Methods Male SPF SD rats were randomly assigned to the sham group,model group,SQBQ group (3. 33 g/kg),and Fosinopril sodium group (1.05 mg/kg). The rat model of heart failure following myocardial infarction was utilized,with the drugs administered via gavage for a continuous 28-day period. The study utilized echocardiography to assess the cardiac structure and function of rats,HE staining to evaluate pathological changes in the myocardium,liquid chromatography-tandem mass spectrometry (LC-MS/MS)to measure plasma TMAO and its related metabolites,and 16S rRNA high-throughput sequencing to observe the intestinal microbial composition and abundance in rats. These analyses were conducted to investigate the correlation between plasma levels of TMAO-related metabolites and differential flora. Results In the model group,significant changes were observed in the cardiac structure,with a notable decrease in cardiac function (P<0.01). Myocardial cells exhibited edema,degeneration,and necrosis,accompanied by infiltration of inflammatory cells in large areas and proliferation of fibrous tissue. Plasma levels of TMAO,trimethylamine (TMA),and γ-butyrobetaine (BBet) were significantly increased (P<0. 05),while choline chloride (Cho) and betaine (Bet) were significantly decreased (P<0. 01). Additionally,the composition of intestinal microbiota exhibited significant changes,with notable decreases in the relative abundances of Bacteroidetes,Actinobacteria,Tenericutes,Bacteroides,Lactobacillus,Allobaculum,and Clostridium (P<0. 05),alongside significant increases in the relative abundances of Proteobacteria,Oscillospira,and Helicobacter (P<0. 05). Additionally,the Firmicutes to Bacteroidetes ratio (F/B Ratio) showed a significant increase (P<0.05). The SQBQ group demonstrated significant improvements in cardiac structure and function in rats (P<0. 05) and mitigated myocardial injury. Plasma levels of TMAO,Cho,Bet,and BBet were found to be inversely regulated (P<0. 05). SQBQ treatment resulted in a significant reversal of the aforementioned changes in gut microbiota composition (P<0. 05) and ameliorated the dysbiosis of intestinal flora. Bacteria such as Bacteroidetes,Helicobacter,F/B ratio,Roseburia,Bacteroides,Allobaculum,and Desulfovibrio were identified as having a strong correlation with the plasma levels of TMAO-related metabolites. Conclusion SQBQ could improve plasma levels of TMAO and its associated metabolites in rats with heart failure,and modulated the composition of gut microbiota involved in TMAO metabolism,contributed to the maintenance of gut microbiota homeostasis,ultimately resulting in improved cardiac function and decreased myocardial damage.