The role of the gut microbiome in sex differences in arterial pressure

Abstract

There has been intense interest in the role of the gut microbiome in human health and a broad range of diseases in recent years. In the context of cardiovascular disease, gut dysbiosis (defined as a change in the gut microbiome and the gut-epithelial barrier) has been linked to disturbances in blood pressure (BP) regulation. These findings build upon our understanding of the complex pathophysiology of essential hypertension. There are clear sex differences in the epidemiology of hypertension, with distinct trends in BP across the life-course in men and women. To date, a role for the gut microbiome in contributing to the sex differences in BP is yet to be clearly established. The purpose of this review is to summarise the current literature regarding how the gut microbiome differs between men and women and to investigate whether sex-determined differences in the gut microbiome influence the response to factors such as diet, obesity and inflammation. Finally, we will explore evidence for the possible interaction between sex-specific factors, including sex hormones and pregnancy, with the gut in the context of hypertension pathophysiology.

Keywords: Arterial stiffness; Blood pressure; Gender; Gut microbiome; Gut microbiota; Hypertension; Preeclampsia; Sex.

Fig. 1

Interactions between blood pressure, sex and the microbiome across the life course. Adapted from Colafella et al. [6]. Compared to men (blue line), women (red line) are usually protected from an increase in blood pressure until they reach menopause. During reproductive years, men have higher BP than women; however, conditions such as PCOS, preeclampsia, obesity and autoimmune and inflammatory diseases, acting partly via the gut microbiome, elevate women’s BP to levels similar to, or greater than, men’s. In postmenopausal years, women’s BP increases sharply relative to men’s, driven by changes in sex hormone levels, alongside metabolic risk factors. Legend: BP, blood pressure; PCOS, polycystic ovarian syndrome

Fig. 2

Mechanisms behind the relationship between the intestinal microbiome and hypertension. Gut dysbiosis (i.e. changes in prevalence of gut microbiota and alterations to the gut epithelial barrier) are characteristic of hypertension. This is modulated by diet, comorbidities, ageing and, likely, gender. Gut dysbiosis can lead to chronic low-grade inflammation, which can result in endothelial dysfunction, increased activity of the classic arm of the renin-angiotensin system and imbalanced salt regulation, contributing to a raise in blood pressure. Legend: RAS, renin-angiotensin system

Fig. 3

Sex differences in determinants, constituents and effects of the gut microbiome. The gut microbiome in men and women diverges after puberty, which is modulated by a range of factors, including sex hormones [57, 58], diet [50, 53] and the impact of metabolic [61, 62] and inflammatory [58] states. The resultant shifts in gut microbiome signature in turn affect inflammation, metabolism and sex hormone levels and contribute to the pathogenesis of obesity, autoimmune disease, PCOS and the development of arterial stiffness. Legend: F/B, Firmicutes/Bacteroides; SCFA, short-chain fatty acids