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Background Chronic heart failure (CHF) affects approximately 26 million people worldwide. Nearly half of CHF patients develop heart failure with preserved ejection fraction (HFpEF), which is associated with myocardial hypertrophy and fibrosis. Although chronic inflammation was suggested as a critical factor contributing to fibrosis development, a new hypothesis of CHF pathogenesis suggested that altered gut microbiota contributes to leaky gut phenotype development and promotes a systemic inflammatory state. CHF patients have an altered gut microbiome. However, the effect of gut microbiota on fibrosis development in HFpEF patients is not yet known. Thus, this clinical study involving HFpEF patients (n = 47) and healthy volunteers (n = 43) intended to identify the correlations between microbiota changes and fibrosis markers in HFpEF patients. Methods We used 16S rRNA metagenomic sequencing to identify the microbiota changes in HFpEF patients. Myocardial fibrosis was quantified using T1 myocardial mapping by using cardiac magnetic resonance. We also assessed the levels of microbial metabolites—trimethylamin N-oxide (TMAO) and short-chain fatty acids (SCFAs)—and measured bloodstream miRNAs and cytokines. The gut microbiome functions were simulated using PICRUSt algorithm. Results The gut microbial communities of HFpEF patients were markedly different from those of healthy individuals. The abundance of Faecalibacterium, Prevotella, and Pseudomonas was significantly decreased, whereas that of Lachnoclostridium, Blautia, Haemophilus, Dorea, Peptococcus, and Tyzzerella was increased in HFpEF patients. These changes could have affected TMAO metabolism and SCFA production: TMAO and hydroxypyruvate levels were significantly higher, whereas isovaleric, methylbutyric, and propionic acids were significantly lower in HFpEF patients than in healthy individuals. The simulation with PICRUSt revealed that genes responsible for starch fermentation, SCFA production, and secondary bile acid metabolism were downregulated. Correlation analysis identified the involvement of microbiota changes and miRNAs 183-3p and 193b-3p. Conclusions Gut microbiome composition shifts in HFpEF patients impair biochemical functions, increase TMAO production, and decrease SCFA biosynthesis. The significant decrease in Faecalibacterium could have the most prominent effect on the host physiology. However, this needs to be determined by conducting experiments on animal models, because the mechanism by which the microbiota is associated with cardiac fibrosis development is not yet known.

Introduction. Helicobacter pylori (Hр) is considered usually as one of the factors in the development of gastritis, peptic ulcer, and gastric cancer, and at the same time as protection from asthma, diabetes type II, and obesity. This study was carried out with a goal to evaluate possible linkage between the levels of circulating anti-Hp antibodies and inflammatory markers - IL-6, IL-8 and malonic dialdehyde (MDA) - in cross-sectional study of Moscow adults. Material and Methods. Serum samples of Moscow working-aged residents (both gender, N=252) were used for evaluation of antibodies to lysate Hp antigen/recombinant CagA and cytokines IL-6, IL-8 with corresponding ELISA kits. MDA was determined by reaction with thiobarbituric acid. Results. Standard correlation analysis didn’t reveal any significant association between the levels of circulating antibodies against the applied commercial antigens and the levels of IL-6, IL-8 and MDA. Nevertheless, two parallel branches of the experimental points in seropositive area of anti-CagA/IL-8 scatterplot (but not for IL-6 and MDA variables) were clearly seen and correspond to two maximums at bimodal anti-CagA distribution. The data obtained are consistent with typical for CagA outstrip in IL-8 induction and testify the existence of two human genotypes having ~2-fold difference in antibody response but the same reactivity of CagA - IL-8 axis. Since CagA-positive IL-8 levels are of one order with CagA-negative ones (from another organs) and signs of concomitant oxidative stress were not revealed, the data obtained can be interpreted equally as early pathologic or actual symbiotic events. Conclusion. Quantitative assessment of circulating anti-Hp antibodies, together with more detail mathematical analysis, will increase contributions of population studies to investigation of equilibrium between Hp and human organisms.

The method of the evaluation of the antioxidant activity (AOA) with a help of stable radical 2,2-diphenyl-1-picrylhydrazyl test (DPPH test) widely applied in pharmacological and food chemistry, was used also in some clinic investigations for the assessment of the total activity of serum low-molecular-weight antioxidants, but never was applied earlier for toxicological and environmental studies. We have developed the new modification of DPPH test, by replacing methanol-based incubation medium to non-ionic water detergent solution, compatible with native blood serum. Modified DPPH test was approved in 5 toxicological experiments on laboratory animals (Gig. Sanit., 2016, 9: 884-90) and in the hygienic study of the influence of ambient air pollution on the health state in a cohort of 142 capable Moscow residents (aged of 43.5 ± 11.8 years). As a results of the cohort observation, AOA of human serum in DPPH test had close to the normal distribution without gender differences, the slowly decrease with age by nearly 0.4% per year and was positively associated with serum concentrations of catabolic antioxidant - uric acid (R=0.257; p=0.002). The influence of outdoor air pollution in the points of the persons permanent homes was studied by 2 methods: 1) dividing Moscow territory into 2 zones accordingly the long-term monitoring of Hydrometereology and Environmental Monitoring Service; 2) by cartographic adjustment of corresponding home buildings to the nearest of 46 route stations of Moscow Agency for Health and Consumer Rights. No significant differences was found between residents of 2 preferred city zones in 12 used serum biochemical markers, the results of DPPH test including. Significant correlation exposure-response was found between the variables “serum AOA in DPPH test” and “benzene annual outdoor concentration” (R=0.342; p=0.00003) by individual exposure evaluation according to the data of route stations. Two main independent predictors of serum AOA values in the observed cohort of Moscow residents (outdoor air benzene and serum uric acid concentrations) detected 14 and 8.5 % of AOA total variance (p = 0.000002 and p =0.00018 correspondingly).