To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3–V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis. NGS analysis was conducted at the family level. No significant differences between patient’s groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota.

Cardiovascular diseases (CVDs) remain the major public health concern worldwide. Over the last two decades, a considerable amount of literature has been published on gut microbiota (GMB) composition and its metabolites, involved in the pathophysiology of CVDs, including arterial hypertension, atrial fibrillation, and congestive heart failure. Although many types of medicines are available to treat CVD, new therapeutic tools are needed to improve clinical outcomes. A challenge that often arises in the researchers’ community is how to manipulate the GMB to manage cardiovascular risk factors. Therapeutic strategies designed to manipulate GMB composition and/or its metabolites include dietary approaches, prebiotics/probiotics supplementation, and fecal microbiota transplantation (FMT). In this review, we have focused on three main cardiovascular pathologies (arterial hypertension, atrial fibrillation and heart failure) due to their shared common pathophysiological pathways and structural changes in myocardium, such as inflammation, hypertrophy, fibrosis, and myocardial remodeling. The main aims of the review are: (1) to summarize current knowledge on the key pathophysiologic links between GMB and CVDs, and (2) discuss the results of the studies on GMB modulation for the prevention and treatment of selected CVDs.

Резолюция экспертного совета “Актуальные вопросы железодефицита в Российской Федерации”

Aim . To study the relationship between the abundance of the genera in the gut microbiota (GM) and levels of serum biomarkers of chronic systemic inflammation and endotoxemia in patients with HFpEF. Material and methods. The composition of GM among 42 patients with HFpEF (men, 57,1%) was assessed by 16S rRNA sequencing. The median age was 67,0 years, interquartile range [64,0; 71,5] years. Correlation and multivariate regression analysis (with adjustments for sex and age) of relationships between the relative abundance of intestinal bacteria and the concentrations of serum biomarkers including high-sensitivity C-reactive protein (hsCRP), interleukins (IL) 1β and 6, the soluble suppressor of tumorigenicity (sST2), and the level of lipopolysaccharide (LPS) was carried out. Results . According to multivariate regression analysis, the relative abundance of Haemophilus was directly related to the concentration of IL-1β (odds ratio (ОR) 32,37, 95% confidence interval (CI) 2,071237,69, p=0,025), Coriobacteriaceae (unclassified) — with IL-6 (ОR 6,27, (1,42-36,74), p=0,024), Porphyromonadaceae (unclassified) — with sST2 (ОR 5,96, (1,33-34,39), p=0,028), and the relative abundance of the genera Pseudomonas (ОR 7,09, (1,45-42,39), p=0,020), Parasutterella (ОR 4,55, (1,07-22,76), p=0,047) and Clostridiaceae (unclassified) (ОR 4,85, (1,06-24,7), p=0,045) was directly associated with LPS levels. Conclusion. In patients with HFpEF, the relative abundance of some GM genera (e.g., Haemophilus , Coriobacteriaceae (unclassified), Porphyromonadaceae (unclassified), Pseudomonas , Parasutterella , Clostridiaceae (unclassified)) is statistically significantly associated with the concentration of biomarkers of chronic systemic inflammation and endotoxemia.

Aim. To study the relationship of gut microbiota (GM) with serum myocardial fibrosis markers in patients with heart failure with preserved ejection fraction (HFpEF).Material and methods. The composition of the gut microbiota among 42 patients with HFpEF aged 67,0 [64,0; 71,5] years (men, 57,1%) was assessed by 16S ribosomal ribonucleic acid sequencing. The quantitative determination of myocardial fibrosis markers was carried out by enzyme-linked immunosorbent assay. Correlation and multivariate regression analysis of relationships between the relative abundance of intestinal bacteria and the concentration of the procollagen type I carboxy-terminal propeptide (PICP) and N-terminal propeptide of procollagen type III (PIIINP) was carried out.Results. The PICP and PIIINP concentrations were 918,0 [700,0; 1032,8] pg/ml and 6,2±2,7 pg/ml, respectively. Correlation analysis revealed a direct relationship between the relative abundance of Allisonella and PICP (r=0,32), as well as Blautia, Enterobаcteriaceae (unclassified) and PIIINP (r=0,37 and r=0,32), p<0,05. The inverse relationship was determined for the relative abundance of the genera Ruminococcus (r=-0,37), Ruminococcaceae (unclassified) (r=-0,31), Gemmiger (r=(-0,35) and PICP, as well as Bilophila and PIIICP (r=(-0,34). Multivariate regression found (normalized coefficient in parentheses) that the abundance of Butyricimonas (0,27) и Blautia (0,35) was directly related to the PICP levels, while the abundance of the genus Intestinimonas ((-0,23) showed an inverse association with the marker level. The abundance of most genera had an inverse relationship with PIIINP: Atopobium (-0,25), Cellulosilyticum (-0,31), Solobacterium (-0,32), Turicibacter (-0,47), Bilophila (-0,30). The directness of the association with PIIINP concentration was demonstrated for the relative abundance of Paraprevotella (0,32) и Desulfovibrio (0,28). The p-value for all associations is <0,05.Conclusion. The relative abundance of GM genera in patients with HFpEF is associated with fibrosis markers (PICP and PIIINP). The results obtained make it possible to deepen the understanding of the relationship between GM and pathogenesis of HFpEF, which may become a step towards understanding the GM role in the progression of left ventricular diastolic dysfunction and rationale for future studies.