Bile acids and salt-sensitive hypertension: a role of the gut-liver axis

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Abstract

Salt-sensitivity of blood pressure (SSBP) affects 50% of the hypertensive and 25% of the normotensive populations. Importantly, SSBP is associated with increased risk for mortality in both populations independent of blood pressure. Despite its deleterious effects, the pathogenesis of SSBP is not fully understood. Emerging evidence suggests a novel role of bile acids in salt-sensitive hypertension and that they may play a crucial role in regulating inflammation and fluid volume homeostasis. Mechanistic evidence implicates alterations in the gut microbiome, the epithelial sodium channel (ENaC), the farnesoid X receptor, and the G protein-coupled bile acid receptor TGR5 in bile acid-mediated effects on cardiovascular function. The mechanistic interplay between excess dietary sodium-induced alterations in the gut microbiome and immune cell activation, bile acid signaling, and whether such interplay may contribute to the etiology of SSBP is still yet to be defined. The main goal of this review is to discuss the potential role of bile acids in the pathogenesis of cardiovascular disease with a focus on salt-sensitive hypertension.

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The global epidemiology of hypertension

Katherine T. Mills, Andrei D. Stefanescu, Jiang Ping He (2020)

Hypertension is the leading cause of cardiovascular disease and premature death worldwide. Owing to widespread use of antihypertensive medications, global mean blood pressure (BP) has remained constant or decreased slightly over the past four decades. By contrast, the prevalence of hypertension has increased, especially in low and middle-income countries (LMICs). Estimates suggest that in 2010, 31.1% of adults (1.39 billion) worldwide had hypertension. The prevalence of hypertension among adults was higher in LMICs (31.5%, 1.04 billion people) than in high-income countries (HICs; 28.5%, 349 million people). Variations in the levels of risk factors for hypertension, such as high sodium intake, low potassium intake, obesity, alcohol consumption, physical inactivity and unhealthy diet, may explain some of the regional heterogeneity in hypertension prevalence. Despite the increasing prevalence, the proportions of hypertension awareness, treatment and BP control are low, particularly in LMICs, and few comprehensive assessments of the economic impact of hypertension exist. Future studies are warranted to test implementation strategies for hypertension prevention and control, especially in low-income populations, and to accurately assess the prevalence and financial burden of hypertension worldwide.

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2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary

Paul K. Whelton, Robert Carey, Wilbert Aronow … (2018)

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Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis

Wei Jia, Weiping Jia, Guoxiang Xie (2017)

Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.