Diet directly affects the host and promotes the growth of bad microbes
High-fat diets damage intestinal cells and alter gut microbiome, causing harmful bacteria growth and production of TMAO, a substance linked to arterial plaque buildup. The mechanism involves impaired mitochondrial function in intestinal cells, which increases oxygen and nitrates that stimulate harmful microbes like E. coli.
- High-fat diets damage intestinal cells and impair mitochondrial function
- Damaged cells produce excess oxygen and nitrates, stimulating harmful bacteria like E. coli
- Harmful bacteria produce trimethylamine (TMA), which the liver converts to TMAO, linked to atherosclerosis
- An existing inflammatory bowel disease drug (5-aminosalicylic acid) restored intestinal cell function in animal studies
- Nearly 40% of the U.S. population is obese, with rates predicted to climb
Researchers discovered that high-fat diets disrupt gut bacteria and intestinal cells, triggering production of a metabolite linked to atherosclerosis and heart disease. A drug used for inflammatory bowel disease showed promise in reversing these harmful changes.
For decades, doctors have known that eating too much fat raises your risk of heart disease. What they didn't know was exactly how the damage happens—the biological chain of events that turns a cheeseburger into arterial plaque. A study published this week in Science offers an answer, and it begins not in the heart itself, but in the gut.
Researchers at Vanderbilt University fed high-fat diets to animals and watched what happened inside their intestines. The results were stark: the fat triggered inflammation and began destroying the cells that line the gut wall. These epithelial cells normally do crucial work—they generate energy through structures called mitochondria, tiny power plants inside each cell. When a high-fat diet damages those mitochondria, the cells start malfunctioning. They produce excess oxygen and nitrates, creating an environment where harmful bacteria thrive.
The shift in the gut's bacterial landscape is the key. Normally, the trillions of microbes living in your intestines exist in a delicate balance with your body, a mutually beneficial arrangement that keeps you healthy. But when harmful bacteria like E. coli flourish in this oxygen-rich, nitrate-rich environment, they begin producing a metabolite called trimethylamine, or TMA. Your liver then converts TMA into a compound called TMAO. This is where the path to heart disease becomes clear: TMAO has been linked to atherosclerosis, the buildup of fatty plaques inside arteries that can lead to heart attacks and strokes.
Mariana Byndloss, an assistant professor at Vanderbilt who co-authored the research, framed the stakes plainly. Nearly 40 percent of Americans are obese, and that number is climbing. Understanding how diet damages the gut-heart connection could reshape how doctors approach obesity and cardiovascular disease. "We show one way that diet directly affects the host and promotes the growth of bad microbes," she said. The researchers had long known that high-fat diets cause dysbiosis—an imbalance in the gut microbiota favoring harmful organisms—but they didn't understand the mechanism. Now they do.
The study also hints at a path forward. When researchers gave the animals a drug called 5-aminosalicylic acid, which is already approved to treat inflammatory bowel disease, it restored function to the damaged intestinal cells and limited the buildup of TMAO. The drug worked even better when combined with probiotics—the beneficial bacteria found in yogurt and supplements that help restore a healthy gut. This suggests that preventing the damage in the first place, or reversing it once it's begun, might be possible through targeted intervention.
Byndloss emphasized that this is still early work, conducted in animals rather than humans. But the implications are significant. If the same mechanism operates in people, it could mean that therapies designed to protect the gut lining and maintain a healthy microbiome might help prevent the cardiovascular damage that follows obesity. The challenge now is understanding whether these findings translate to the human body, and whether a drug-and-probiotic combination could actually reduce heart disease risk in people who eat high-fat diets. That work will take time, but for the first time, researchers have a clear picture of how the damage happens—and that's the first step toward stopping it.
Citações Notáveis
We show one way that diet directly affects the host and promotes the growth of bad microbes.— Mariana Byndloss, Vanderbilt University Medical Center
Only by fully understanding the relationship between the host and gut microbes during health and disease are we going to be able to design therapies that will be effective in controlling obesity and obesity-associated outcomes like cardiovascular disease.— Mariana Byndloss
A Conversa do Hearth Outra perspectiva sobre a história
So the gut bacteria are the culprit here? We've been blaming fat all along?
Not exactly. The fat is still the trigger. But the bacteria are the mechanism—the way the damage actually gets to your heart. Without understanding that chain, you're just telling people to eat less fat without knowing why it matters.
Walk me through it again. High-fat diet damages cells, cells produce oxygen, oxygen feeds bad bacteria—and then what?
Those bad bacteria make a substance called TMA. Your liver turns it into TMAO, which sticks to your arteries and builds up as plaque. That's atherosclerosis. That's the heart attack waiting to happen.
And they found a drug that stops this?
A drug that's already being used for something else entirely—inflammatory bowel disease. It fixed the damaged intestinal cells in the animals. Combined with probiotics, it looked even more promising.
Why does that matter? Why not just tell people to eat less fat?
Because some people won't, or can't, or don't know they're doing it. If we can interrupt the damage at the gut level, we might be able to prevent the heart disease even if the diet doesn't change. That's the real possibility here.
Is this proven in humans yet?
No. This is animal research. But it's the first time anyone has actually mapped out how the damage happens. That's the foundation everything else builds on.