Intestinal bacteria that live in our gut can have a surprising influence on how fast our blood vessels age and whether we develop heart disease. In a recent study, researchers found that as we grow older, certain microbes produce higher levels of a compound called phenylacetic acid. This substance can make the cells lining our blood vessels stop dividing, release inflammatory signals, and take on traits of aged cells. Over time, these changes cause vessels to stiffen and work less effectively, setting the stage for cardiovascular problems.
Our intestines are home to tens of trillions of bacteria, and most of them help break down the food we eat into smaller molecules. While we have come to appreciate that these microbes can affect digestion and immunity, it turns out they also influence the health of our blood vessels. By analyzing data from over 7,000 healthy people aged 18 to 95, together with experiments in aging mice, the researchers noticed that blood levels of phenylacetic acid steadily rose with age. This hinted that the gut microbiome might be sending signals that accelerate vascular aging.
To understand exactly how phenylacetic acid affects vessel cells, the team turned to lab experiments. They exposed endothelial cells, the thin layer of cells that lines every blood vessel, to amounts of phenylacetic acid similar to what’s seen in older individuals. Within days, these cells showed signs of senescence: they stopped multiplying, started producing molecules that promote inflammation, and exhibited markers typical of old cells. As a result, the vessel walls would likely become less flexible and more prone to damage.
Delving deeper, the scientists used genetic and computational tools to pinpoint the exact gut microbe responsible for producing phenylacetic acid. They identified a specific strain called Clostridium sp. ASF356, which takes the amino acid phenylalanine (found in protein-rich foods) and converts it into phenylacetic acid.
When young mice were given this bacterium, their bodies accumulated more phenylacetic acid and their blood vessels began showing features of aging. When the researchers removed the bacteria using antibiotics, phenylacetic acid levels dropped—and the signs of vessel aging receded.
Not all gut-derived substances harm our vessels, however. The same team discovered that another class of compounds, called short-chain fatty acids (SCFAs), actually helps keep blood vessels healthy. When we eat foods rich in dietary fiber, like whole grains, fruits, and vegetables, our gut bacteria ferment those fibers and produce SCFAs such as acetate. Lab tests showed that adding sodium acetate to aged endothelial cells could restore their ability to function normally, even reversing some signs of senescence. This suggests that a diet high in fiber can promote the production of these “good” bacterial products, acting like a natural fountain of youth for our vessels.
As people grow older, the mix of gut bacteria changes: strains that produce beneficial SCFAs decline, while those that make phenylacetic acid become more common. This imbalance can tilt the body toward inflammation and vascular aging.
In real-world terms, diets high in red meat, dairy, and certain artificial sweeteners, foods rich in phenylalanine, may feed the harmful bacteria, raising phenylacetic acid levels. On the other hand, a fiber-rich, plant-based diet supports acetate-producing microbes that counteract vessel aging.
The researchers are now exploring ways to tip the gut ecosystem back in favor of health. One idea is to develop probiotics or genetically modified bacteria that reduce phenylacetic acid production. Early lab tests have been promising, suggesting it may be possible to block the formation of this harmful compound within the intestine. Meanwhile, simple dietary changes like choosing more whole grains, legumes, and vegetables can boost the numbers of bacteria that make beneficial SCFAs, helping to maintain younger, more flexible blood vessels.
By uncovering how intestinal microbes drive the aging of blood vessels, this study highlights a whole new angle on preventing heart disease. It shows that we are not only what we eat, but also what our gut bacteria produce from our meals. As research continues, targeting the gut microbiome may become a key strategy for keeping our blood vessels youthful and reducing the risk of cardiovascular disease.
The research paper has been published in Nature Aging.
