NIH Grant Backs UToledo Study of Gut Bacteria, Estrogen and Blood Pressure

NIH Grant Backs UToledo Study of Gut Bacteria, Estrogen and Blood Pressure

Give a common gut bacterium to male rats with high blood pressure, and their blood pressure drops. Give it to females, and it rises.

A University of Toledo researcher has received a two-year, $401,618 grant from the National Institute on Aging, part of the National Institutes of Health, to find out why, and whether estrogen is the reason.

Dr. Tao Yang, associate professor in the Department of Physiology and Pharmacology in the College of Medicine and Life Sciences, is studying Akkermansia muciniphila, a microscopic resident of the gut that may respond to estrogen and affect blood pressure differently depending on sex.A. muciniphila naturally lives in the intestines and feeds on the mucus that lines the intestinal tract. Earlier research suggests the bacterium can support the gut's protective barrier and improve measures of metabolic health, and it has gained attention as a potential next-generation probiotic.

Yang's new research builds on his work showing that A. muciniphila responds directly to estrogen. In a 2023 study, Yang and colleagues found that the bacterium was more abundant in female mice with intact ovaries and that its growth increased in the presence of estrogen.

That finding led Yang's team to ask a larger question: Could the bacterium also affect blood pressure differently in males and females? Early results suggest it does, in opposite directions.

"Our studies show that A. muciniphila is more abundant in female than male hypertensive rats, but greater abundance does not necessarily mean greater benefit," Yang said. "In our preliminary experiments, giving live bacteria lowered blood pressure in males but raised it in females. We are now investigating whether sex hormones explain these opposite responses."

The work comes as scientists increasingly study the gut microbiome, the community of bacteria and other microorganisms living in the digestive tract, for its connection to health and disease. Research has found differences in the gut microbiome between people with high blood pressure and those with normal blood pressure. Gut bacteria can influence blood pressure through effects on the intestinal barrier, immune system and kidneys, as well as through the substances the bacteria produce.

The new project will focus on how estrogen acts directly on A. muciniphila and why the bacterium produces different blood pressure responses in males and females.

Yang will collaborate with Dr. John Bellizzi, professor of chemistry and biochemistry, to study the structure of a previously uncharacterized protein in A. muciniphila and determine whether it plays a role in the bacterium's sex-specific effects.

The project will also give UToledo graduate students hands-on research experience with bacterial culture, protein expression and purification, gene expression measurements, animal studies, and tissue collection.

The research could have implications for understanding blood pressure as people age. Blood pressure often increases with age, and hormonal changes during menopause can further affect cardiovascular health. Yang hopes understanding the relationship between sex hormones, the gut microbiome and blood pressure could eventually help researchers develop more personalized approaches to treating hypertension.

Asked whether the bacterium could someday be used to prevent or treat high blood pressure, Yang was cautious.

"Potentially, yes, but it is too early to know whether A. muciniphila can safely and effectively prevent or treat hypertension in people," he said. "Our preliminary findings suggest that its effects on blood pressure may differ between males and females, so understanding who might benefit is essential."

By the end of the two-year project, Yang hopes to establish whether the different responses seen in male and female rats can be reproduced and to identify the biological mechanisms behind them.

"We want a clearer understanding of when this bacterium may be beneficial and when it may have unfavorable effects," Yang said. "That knowledge would provide a foundation for future human studies that account for sex and hormonal status."