Virwani PD, Qian G, Hsu MSS, Pijarnvanit TKKTS, Cheung CN, Chow YH, Tang LK, Tse YH, Xian JW, Lam SS, Lee CPI, Lo CCW, Liu RKC, Ho TL, Chow BY, Leung KS, Tsang HW, Lo EKK, Tung KTS, Chung SK, Yuen MF, Leung SY, Ip P, Hung IF, Louie JCY, El-Nezami H, Ho JWK, and Lau KK
Background: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension., Methods: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years)., Results: The hypertensive group was associated with GM alterations; however, significant differences in β-diversity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically, Ruminococcus gnavus , Clostridium bolteae , and Bacteroides ovatus were significantly more abundant in the hypertensive women, whereas Dorea formicigenerans was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men., Conclusions: GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension., Competing Interests: Disclosures K.K. Lau received grants from Research Fund Secretariat of the Food and Health Bureau, Innovation and Technology Bureau, Research Grants Council, Amgen, Boehringer Ingelheim, Eisai, and Pfizer and consultation fees from Amgen, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi, all outside the submitted work. S.Y. Leung has received research sponsorship from Pfizer, Merck, Servier, and Curegenix. S.K. Chung received a faculty research grant (FRG-22-024-FMD) and Dr Neher’s Biophysics Laboratory for Innovative Drug Discovery from the Macao Science and Technology Development Fund (FDCT project code: 001/2020/ALC), all outside of the submitted work. The other authors report no conflicts.