Zhongguo quanke yixue (Oct 2023)
Study on the Changes of Intestinal Flora and Its Metabolite Phenylacetylglutamine in Patients with Chronic Heart Failure
Abstract
Background The intestinal flora and its metabolites play an important role in the pathology of chronic heart failure (CHF), which is a severe manifestation or terminal stage of various cardiovascular diseases. Increasing evidence has shown that dysbiosis of the intestinal flora and its metabolites can lead to bacterial translocation, release of mediators, inflammatory response and consequently aggravation of CHF. Objective To analyze the changes of intestinal flora and its metabolite phenylacetylglutamine (PAGln) in patients with CHF and explore the role played by gut microbiota in heart failure. Methods A total of 58 patients with heart failure admitted to the Department of Cardiology of the South Branch of the Sixth People's Hospital of Shanghai Jiaotong University were selected as the CHF group, and 46 patients with the same CHF risk factors but without clinical symptoms and past medical history of CHF were selected as the control group from June 2021 to June 2022. Plotting ROC curves of brain natriuretic peptide (BNP) and PAGln for the diagnosis of CHF. The abundance and diversity of intestinal flora in the two groups were analyzed using 16S rRNA sequencing. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to detect PAGln concentrations in the plasma of samples from both two groups. Results The left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), BNP, and PAGln in the CHF group were higher than the control group, and the left ventricular ejection fraction (LVEF) was lower than the control group (P<0.05). The area under curve (AUC) of BNP and PAGln levels for the diagnosisof CHF patients was 0.995 and 0.913, respectively. Venn diagram showed that the number of OTUs specific to the CHF group was less than the control group. Alpha diversity analysis showed that the Chao1 index was lower in the CHF group than the control group (P<0.05). β diversity analysis showed that the overall structure of the intestinal flora differed between the two groups. At the genus level, the relative abundances of Escherichia-Shigella, Megamonas, Klebsiella, Bifidobacterium, Parabacteroides, and Romboutsia were higher in the CHF group than the control group (P<0.05), and the relative abundances of Solimonas and Dorea were lower than the control group (P<0.05). The results of LEfSe analysis showed that Lachnospiraceae, Solimonadaceae, Solimonas, Dorea, and Burkholderiaceae were elevated in the control group (P<0.05), and Enterobacteriaceae, Escherichia, Bifidobacterium, Bifidobacteriaceae, Klebsiella, Lactobacillaceae, Lactobacillus, Megamonas, Rikenellaceae, Alistipes, Parabacteroides, and Tannerellaceae were elevated in the CHF group (P<0.05). Typical correlation analysis (CCA) showed that BNP, PAGln, LVEDD, and LVESD were significantly correlated with the CHF group, with BNP having the greatest effect on community changes. Correlation analysis showed that Escherichia-Shigella was positively correlated with BNP and PAGln (P<0.05) ; Bacteroides was negatively correlated with BNP; Romboutsia, Fusobacterium, and Phascolarctobacterium were negatively correlated with BNP and PAGln (P<0.05) . Conclusion The structural composition of the intestinal flora in patients with CHF was significantly different from the patients with the same co-morbidities but without clinical manifestations and previous medical history of CHF, with a decrease in flora diversity and a significant increase in the abundance of pathogenic intestinal bacteria, which may lead to an increase in the level of PAGln in CHF patients and participate in the development of CHF.
Keywords
