Table 1 Questions for further research into the role of the microbiome in mediating sex differences in blood pressure

 Is the intestinal microbiome different between hypertensive women and men?

Studies of intestinal microbial signatures in men and women with normal blood pressure, pre-hypertension and hypertension.

 Does the gut microbiome change with menopause in women, and parallel changes in blood pressure?

Longitudinal studies of women starting prior to menopause.

 Can HRT after menopause affect the intestinal microbiome?

Cross-sectional studies of women grouped according to HRT use.

 Does the modulating effect of obesity and metabolic syndrome on blood pressure in pre-menopausal women act via the microbiome?

Studies of pre-menopausal women including cohorts of hypertensive obese and normotensive obese women.

 What is the role of the intestinal microbiome in driving hypertension and cardiovascular complications of PCOS?

Studies of women with PCOS within and without hypertension and cardiovascular sequelae.

 How does the microbiome change across the spectrum of normotensive pregnancies, gestational hypertension and preeclampsia?

Studies of women at a similar stage of pregnancy with and without these disorders.

 Can the microbiome of women with PCOS or hypertensive disorders of pregnancy induce hypertension?

Animal models/germ-free experiments using microbial transfer from affected women.

 Is arterial stiffness greater in ageing women as a result of changes to their gut microbiome signature?

Correlation of PWV, hypertension and ventricular-vascular coupling with α and β diversity in men and women.

 Does the gut microbiome play a role in determining the development of HFpEF vs. HFrEF in women vs. men?

Studies of microbial signatures in patients with HFpEF and HFrEF, stratified by gender.

 Is greater ventricular remodelling and diastolic dysfunction in response to hypertension related to the microbiome in women?

Studies correlating α diversity with left ventricular geometry and haemodynamics in hypertensives and controls across both sexes.

 To what extent does inflammation mediate the relationship between the microbiome, sex differences in hypertension and its complications?

Investigation of immune activation and inflammatory cytokines, and correlation with microbial signatures and complications in hypertensive men and women.