1. Introduction
obesity, CVDs, hyperoxic, endothelial injury, liver steatosis, hypoxia, cardiovascular and metabolic diseases, TMA, metabolic syndrome, atherosclerosis, T2DM, steatohepatitis
OBESITY, DIASTOLIC DYSFUNCTION, CARDIOVASCULAR DISEASES, CVD, HYPOXIA, LIVER STEATOSIS, HYPERTENSION, DYSFUNCTION, MULTIPLE PATHOLOGIES, HYPOXIC, INSULIN RESISTANCE, REGRESSION, METABOLIC SYNDROME, ATHEROSCLEROSIS, PATHOLOGY, DISEASES, STEATOHEPATITIS
Along with the known risk factors of cardiovascular diseases (CVDs) constituting metabolic syndrome (MS), the gut microbiome and some of its metabolites, in particular trimethylamine-N-oxide (TMAO), are actively discussed. A prolonged stay under natural hypoxic conditions significantly and multi-directionally changes the ratio of gut microbiome strains and their metabolites in feces and blood, which is the basis for using hypoxia preconditioning for targeted effects on potential risk factors of CVD. A prospective randomized study included 65 patients (32 females) with MS and optimal medical therapy. Thirty-three patients underwent a course of 15 intermittent hypoxic–hyperoxic exposures (IHHE group). The other 32 patients underwent sham procedures (placebo group). Before and after the IHHE course, patients underwent liver elastometry, biochemical blood tests, and blood and fecal sampling for TMAO analysis (tandem mass spectrometry). No significant dynamics of TMAO were detected in both the IHHE and sham groups. In the subgroup of IHHE patients with baseline TMAO values above the reference (TMAO ≥ 5 μmol/l), there was a significant reduction in TMAO plasma levels. But the degree of reduction in total cholesterol (TCh), low-density lipoprotein (LDL), and regression of liver steatosis index was more pronounced in patients with initially normal TMAO values. Despite significant interindividual variations, in the subgroup of IHHE patients with MS and high baseline TMAO values, there were more significant reductions in cardiometabolic and hepatic indicators of MS than in controls. More research is needed to objectify the prognostic role of TMAO and the possibilities of its correction using hypoxia adaptation techniques.The effect of the gut microbiome, which has been described as a separate organ in some studies, on cardiometabolic pathology (atherosclerosis, hypertension, obesity, insulin resistance (IR)) is now well established [In particular, elevated plasma levels of TMAO have been shown to be associated with diastolic dysfunction, contributing to the development of early vascular atherosclerosis through accelerating endothelial injury and dysfunction [Recent data demonstrate the potential role of the gut microbiota as a pathogenic factor associated with metabolic syndrome (MS). Qualitative and quantitative changes in the gut microbiota are associated with various clinical conditions, such as obesity, insulin resistance and T2DM, and steatohepatitis [Given the significant potential involvement of TMAO in the development of cardiovascular and metabolic diseases, there is an active search for TMAO inhibitors. No direct inhibitors of TMAO have yet been found, but the compounds 3,3-dimethyl-1-butanol (DMB) and resveratrol are known to inhibit TMAO formation and its negative effects. Through inhibiting the formation of TMA by gut microbes, DMB thereby reduces plasma TMAO levels and also attenuates the development of atherosclerosis caused by a diet high in choline [In addition, it was found that episodes of “acute” hypoxia as well as a prolonged stay under conditions of medium-high altitude significantly and multi-directionally change the ratio of intestinal microbiome strains and their metabolites in feces and blood [Intermittent normobaric hypoxic–hyperoxic exposures (IHHEs), as one of the variants of the technology of adaptation to periodic hypoxia in recent years, are actively used in the treatment and complex rehabilitation of patients with multiple pathologies and comorbidities [Interval hypoxic–hyperoxic training procedures are a new approach in which the patient’s breathing through an oronasal mask with a hypoxic gas mixture is alternated with episodes of breathing with a hyperoxic mixture (FiOIntermittent hypoxic conditioning and IHHE, as one of effective hypoxic conditioning protocols, have been used in rehabilitation courses for a wide number of different diseases, but no studies have shown any significant adverse side effects [The aim of this pilot study was to evaluate the possible effects of IHHE on the metabolic product of the intestinal microbiome (TMAO) and the relationship of its dynamics with cardiometabolic risk factors and components of MS.