219Serum Trimethylamine N-Oxide levels and 16S rRNA gut microbiota profiling in patients with heart failure and preserved ejection fraction and healthy individuals

Abstract Introduction Recent evidence suggests the role of gut microbiota dysregulation in the pathophysiology of chronic heart failure (HF). Elevated levels of Trimethylamine N-Oxide (TMAO) have shown to increase the risk of cardiovascular events and HF. Among patients with HF and preserved ejection fraction (HF-pEF) the link between TMAO levels and ventricular fibrosis was observed in studies, however, the data regarding 16S rRNA microbiome profiling in this particular group of HF are lacking. Purpose The research was aimed at investigating the gut microbiome diversity and composition as well as the serum TMAO levels among two groups of patients: healthy controls (HC) and HF-pEF. Methods 44 patients with HF-pEF and 45 HC with body mass index <35 kg/m2, no history of acute coronary syndrome, myocardial infarction or diabetes were enrolled in the study. All patients underwent transthoracic echocardiography with Doppler study to exclude diastolic dysfunction (E/e' <8 cm/s) or to prove HF-pEF (according to the recent ESC guidelines based on E/e' ratio, N-terminal pro-B type natriuretic peptide >125 pg/ml and symptoms of HF). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. TMAO levels were determined by liquid chromatography tandem mass spectrometry. Results The age in HC was 57,5 [48; 63] (28% men), age in HF-pEF group was 67 [64; 74] years (52% men). The serum concentration of TMAO in HC was 3.72 uM, in HF-pEF was 5.24 uM. The group of HF-pEF had significantly higher levels of the marker, p=0,003. Bacterial communities of both groups were dominated by the Firmicutes and Bacteroidetes phyla. The most abundant genus in both groups were Bacteroides. The Shannon index, the Chao 1 estimator, and the Simpson index assessing α diversity were not significantly different between groups. However, Bacteroides, Alistipes, Pseudomonas, and Fusobacterium were enriched in the common core microbiota of HF-pEF patients, while Lachnospira, Roseburia, Eubacterium, Methanobrevibacter and Faecalibacterium were depleted. To note, Lactobacillus and Bifidobacterium were depleted in HF-pEF patients too. TMAO levels in HC and HF-pEF groups Conclusions We have shown significant structural alterations of the intestinal microbiome and increased TMAO levels in HF-pEF patients' serum compared to HC. These findings may enable deeper understanding of the complex multifactorial pathogenesis of HF-pEF for the future development of personalized microbiome-based diagnostics and therapies for individuals at risk.