Dietary metabolism, the gut microbiome, and heart failure

Abstract

The contribution of gut microbiota to human health and diseases has expanded our insights into how microbial composition and function impacts the human host. Heart failure has long been associated with splanchnic circulation congestion, leading to bowel wall edema and impaired intestinal barrier function. This is thought to heighten the overall inflammatory state via enhanced bacterial translocation and the presence of bacterial products in the systemic circulation. Recently, several metabolites produced by gut microbes from dietary metabolism have also been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity and type 2 diabetes mellitus. These findings suggested that the gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly impact host physiology. We will discuss several newly discovered gut microbial metabolic pathways, including the production of trimethylamine (TMA)/ trimethylamine N-oxide (TMAO), short-chain fatty acids, and secondary bile acids, that appear to participate in the development and progression of cardiovascular diseases, including heart failure. We will also discuss the gut microbiome as a novel therapeutic target for the treatment of cardiovascular disease, and potential strategies for targeting intestinal microbial processes.

Measurement of gut microbial metabolites in cardiometabolic health and translational research

“…The identification of TMAO as a CVD‐relevant biomarker is a notable example of a disease‐relevant microbial metabolite discovery. By using an untargeted metabolomic approach, Hazen et al identified dozens of metabolites, including choline, TMA, and TMAO – which were significantly different in the cases of CVD compared with age‐ and gender‐matched controls – and confirmed their observations by using several validation cohorts . They then proved that the identified metabolites are from a gut microbiota‐dependent pathway by using traceable isotope‐labeled compounds in animal studies and by establishing the causal role of TMAO in atherogenesis and thrombosis in animal and cell models.…”

“…40 Both indoxyl sulfate and FIGURE 1 Crosstalk between gut microbial metabolites and organs beyond the gut through the gut-systemic axis ↑foam cell formation, ↓reverse cholesterol transport, ↑platelet aggregation potential. Target receptor remains unknown 33,34 Indoxyl sulfate Tryptophan Uremic toxin proposed to aggravate chronic renal disease, CVD, as well as CKD related bone disorders 21,35 Enter proximal renal tubular cell through organic anion transporter and cause oxidative stress by activating ROS system 21,35 p-Cresol sulfate Tyrosine, phenylalanine…”

Novel Basic Science Insights to Improve the Management of Heart Failure: Review of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology

“…Several relatively small studies in patients have attempted to characterize HF gut microbiota profile, even if inconsistencies and discrepancies have also been outlined [82]. Since gut microbial transplantation has been already proven to provide diseases Alterations in gut permeability, changes in diversity and composition of gut microbiome and elevated circulating levels of LPS have been already identified in patients with HF, triggering a state of chronic inflammation [84,87,88]. Several relatively small studies in patients have attempted to characterize HF gut microbiota profile, even if inconsistencies and discrepancies have also been outlined [82].…”

Developmental Pharmacodynamics and Modeling in Pediatric Drug Development

“…Host microbes have been shown to bolster or suppress the effects of fluoropyrimidines, a treatment for colorectal cancer with highly variable efficacy . Moreover, the gut microbiome secretes bioactive metabolites, like short‐chain fatty acids, amino acid metabolites, and secondary bile acids, which may modulate disease progression . Changes in the microbiome secondary to tuberculosis treatment may impact the course of disease .…”

“…48 Moreover, the gut microbiome secretes bioactive metabolites, like short-chain fatty acids, amino acid metabolites, and secondary bile acids, which may modulate disease progression. 49 Changes in the microbiome secondary to tuberculosis treatment may impact the course of disease. 50 These studies point to the possibility of developmental changes in the microbiome affecting the variability of PD.…”