Gut Microbiota in Cardiovascular Health and Disease

Abstract

Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through a number of pathways, including the trimethylamine (TMA)/ trimethylamine N-oxide (TMAO) pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these “metabolism dependent” pathways, metabolism independent processes are suggested to also potentially contribute to CVD pathogenesis. For example, heart failure associated splanchnic circulation congestion, bowel wall edema and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are believed to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.

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.…”

“…However, these nutrients can be utilized by microbes in the gut to produce trimethylamine (TMA) as a byproduct. The TMA absorbed from the gut is then oxidized into TMAO in the liver and has proven to be a strong risk factor for cardiovascular disease (CVD) . The amino acids ingested from dietary intake were generally regarded as materials for our body to synthesize enzymes and proteins, but they can be metabolized earlier by the gut microbes before their absorption into the gut.…”

“…For example, TMA with a fish‐like odor from microbial metabolism of carnitine and choline in the gut is oxidized to odorless TMAO by flavin monooxygenase in the liver. TMAO in the circulatory system is then excreted through urination . In individuals with normal renal function, the efficient urinary excretion of TMAO keeps a low level of average blood TMAO.…”

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

“…On the one hand, the intestinal bacteria contribute to host health by providing macro-and micro nutrients such as simple carbohydrates e.g. lactose (the core of the HMOS), amino acids, and vitamins; the inhibition of pathogens by competitive exclusion; maintenance of gut immune function; maintenance of normal gut motility; and the prevention of cancer and cardiovascular disease (Brennan and Garrett 2016, Honda and Littman 2016, Kamada et al 2013, Quigley 2011, Rowland et al 2018, Tang et al 2017. On the other hand, an aberrant gut microbiota is associated with diseases including cardiovascular diseases, metabolic syndrome, non-alcoholic fatty liver diseases, obesity, type 2 diabetes, and inflammatory bowel diseases (de Vos and de Vos 2012).…”

Avaliação da atividade imunoterapêutica do probiótico LLHsp65 na asma experimental

“…Adicionalmente, a maior exposição à alérgenos contribui para a polarização da resposta imunológica para o tipo Th2, causando uma desregulação no balanço homeostático Th1/Th2, aumentando assim a probabilidade do desenvolvimento de doenças alérgicas (Sult et al, 2003;Eder, Ege and von Mutius, 2006). Em adição a essa hipótese, muitos estudos vêm demonstrando que o desequilíbrio da interação microbiota--hospedeiro aumenta a suscetibilidade à diversas doenças como a artrite (Taneja, 2014), esclerose múltipla (Bhargava and Mowry, 2014), aterosclerose (Org, Mehrabian and Lusis, 2015), infecções intestinais (Ross, Spinler and Savidge, 2016), doenças cardiovasculares (Tang, Kitai and Hazen, 2017), diabetes mellitus (Tai, Wong and Wen, 2015) e as doenças alérgicas (Gigante et al, 2011;Herbst et al, 2011;Kang, Cai and Zhang, 2016;Losses and Larger, 2016).…”