High fat diet, gut bacteria, and heart disease: Exploring the connection

 

• A high fat diet disrupts the inner workings of the gut, and this may contribute to cardiovascular disease risk, according to a recent study.
• The researchers investigated the link between greasy diets, gut microbes, and the risk of developing heart diseases in mice.
• The findings may shed light on the exact mechanism through which high fat diets increase the risk of cardiovascular diseases — and how to prevent these negative outcomes.

A high fat diet, such as one that includes plenty of fast food, increases the risk of cardiovascular diseases. This type of diet interferes with normal functioning in the gut and promotes the growth of harmful microbes.

In addition, gut microbes convert chemicals in fatty foods into a harmful metabolite that promotes atherosclerosis — a disorder in which the formation of plaques narrows the arteries.

Until recently, scientists were unsure of the exact mechanism through which gut microbes caused heart diseases. Now, researchers at Vanderbilt University Medical Center, in Nashville, TN, have set out to explain this phenomenon.

Their findings appear in the journal Science.

Diet, microbiota, and heart disease

As the World Gastroenterology Organisation explains, the food we eat has complex interactions with the gut, including its microbiota.

The gut microbiota plays an important role in human health and the prevention of disease. As a result, changes in its regular functioning may play a part in some medical conditions, such as irritable bowel syndromeTrusted Source, obesityTrusted Source, and cardiovascular diseasesTrusted Source.

Before now, scientists had often wondered about the link between the intestines, gut microbes, and health outcomes.

Dr. Mariana Byndloss and her team at the Vanderbilt University Medical Center suggest answers to this puzzle.

Their research in mice reveals that chronic exposure to a high fat diet damages the intestinal epithelium and causes low grade inflammation. It also shows that a high fat diet interferes with the energy-generating functions of the mitochondria.

Dr. Byndloss told Medical News Today that her team’s research was inspired by a previous study that showed the negative effect of high fat diets on the gut and the gut microbiota.

“[Based on previous studies], we hypothesized that the damage to the intestinal mucosa caused by a high fat diet could be driving negative changes to the gut microbiota, including expansion of harmful bacteria (e.g., Enterobacteriaceae) and promoting disease,” she said.

“Our research is finding that the host cells, specifically the intestinal epithelium, play a crucial role in modulating microbiota function, and can ‘turn on’ or ‘turn off’ metabolic pathways in the microbes that will directly affect risk for certain diseases,” Dr. Byndloss added.

This supports previous studies that show that a healthy intestinal epithelium is important in supporting beneficial microbes and maintaining intestinal health.

Dr. Byndloss stressed the need for a complete understanding of the relationship between human hosts and gut microbes.

She explains, “Only by fully understanding the relationship between the host — us — 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.”

Testing hypotheses 

The scientists employed animal models in testing their hypotheses. First, they noticed that in high fat diets, gut microbiota converted dietary choline to trimethylamine. This was further converted to trimethylamine N-oxide (TMAO) by the liver.

TMAO alters cholesterol metabolism, leading to the formation of plaque deposits in the arteries — which results in atherosclerosis.

Next, the team noted that a high fat diet disrupted the regular functions of the mitochondria, leading to increased oxygen and nitrate production. Consequently, these gases fueled the growth of potentially disease-causing Enterobacteriaceae microbes, such as Escherichia coliTrusted Source.

These findings confirmed the researchers’ hypotheses about the role of high fat diets on disease outcomes. It also explained precise mechanisms through which these diseases might occur.

And in a key finding, the researchers demonstrated that after treatment with the drug 5-aminosalicylic acid, normal mitochondria oxygen and nitrate levels were restored. Furthermore, the drug also slowed the increase in circulating TMAO in the animal models.

While these results are intriguing, the researchers acknowledge that their study had limitations. First, they conducted their research in mouse models, not human participants. Second, the study did not show an increase in cardiovascular disease. This is because it required specific mouse lines that were unavailable due to the COVID-19 pandemic.

However, there are plans for follow-up studies to demonstrate that an increase in TMAO due to a high fat diet directly promotes atherosclerosis and cardiovascular diseases.

Dr. Byndloss and her team also plan to explore the role of the host-microbe relationship in the development of other diseases. And their first area of interest might be colorectal cancer.

Until then, they are pleased that their study has been able to demonstrate how dietary choices may be promoting the survival of harmful microbes in the gut.

Source: Medical News Today