Health & Wellbeing

How gut bacteria pave the road from high-fat diet to heart disease

How gut bacteria pave the road...
New research describes a mechanism by which diet can damage intestinal cells, setting off a chain reaction leading to microbiome dysfunction and heart disease
New research describes a mechanism by which diet can damage intestinal cells, setting off a chain reaction leading to microbiome dysfunction and heart disease
View 1 Image
New research describes a mechanism by which diet can damage intestinal cells, setting off a chain reaction leading to microbiome dysfunction and heart disease
New research describes a mechanism by which diet can damage intestinal cells, setting off a chain reaction leading to microbiome dysfunction and heart disease

Robust new research, published in the journal Science, has revealed a microbial mechanism connecting obesity with heart disease. The study describes how a high-fat diet damages intestinal cells, leading to an imbalance of bad bacteria that produce metabolites known to contribute to cardiovascular disease.

The new findings build on several previous studies to finally present a complete picture of the relationship between diet, gut bacteria and heart disease. Prior research has shown gut bacteria and the health of intestinal tissue share a close relationship.

When the epithelial cells that line our intestines are inflamed, our gut microbial populations can fall out of balance. And this microbiome imbalance, known as dysbiosis, leads to excessive production of certain metabolites that increase one’s risk of atherosclerosis. But there was still one missing link in that chain reaction researchers had not fully uncovered.

"It was known that exposure to a high-fat diet causes dysbiosis – an imbalance in the microbiota favoring harmful microbes, but we didn't know why or how this was happening," explains Mariana Byndloss, a researcher from Vanderbilt University Medical Center working on the new study. "We show one way that diet directly affects the host and promotes the growth of bad microbes."

Using mouse models the new research showed how a high-fat diet impairs the activity of mitochondria in intestinal epithelial cells. This diet-induced damage leads to those cells producing excessive volumes of oxygen and nitrate.

Certain harmful gut microbes such as E. coli thrive in high oxygen and nitrate environments, so this helps them increase in numbers and intensify production of a metabolite called trimethylamine (TMA). The liver then oxidizes TMA, converting it into trimethylamine-N-oxide (TMAO), a compound increasingly implicated in cardiovascular disease.

The researchers then went one step further, investigating whether protecting those intestinal epithelial cells could stop this entire high-fat diet-induced chain of events. They turned to a drug called 5-aminosalicylic acid (5-ASA), used for over 30 years to help reduce intestinal inflammation in subjects with inflammatory bowel disease.

In mouse models 5-ASA helped restore normal mitochondrial function in intestinal cells. This then lowered the downstream increase in TMAO previously triggered by a high-fat diet.

Byndloss says this is compelling proof-of-concept evidence showing it is possible some of the negative outcomes of a high-fat diet can be prevented. In the future, Byndloss notes, it could be possible to use drugs like 5-ASA alongside probiotics to help maintain healthy gut bacterial populations and limit the negative effect of high-fat diets on the heart.

"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,” says Byndloss.

The new study was published in the journal Science.

Source: Vanderbilt University Medical Center

I'm not sure if it is the author of this article, here, or the report that is in error but a "high fat diet" does not equal "obesity". It is excess carbohydrate consumption that primarily causes obesity. I accept that most people are still *mind-numbingly* oblivious of this fact (blame the deliberately misleading marketing by the food industry with the collusion of moronic/corrupt politicians) but you'd like to think that someone taking such an article to the internet would know!
Kyle McHattie
This study is a garbage opinion based study. There are many controlled and peer reviewed studies recently that completely debunk this ridiculous conclusion. Fat is not the enemy. Sugar is the enemy and when this is reviewed they will have to retract. I guarantee that when we find out who funded this study, it will be one of the sugar companies.
Thanks Rich - great synopsis. This mouse study is rather half-ass research but you do it more than justice. Almost everyone in medicine knows what you eat can have a positive and/or negative impacts on your alimentary system. Leaky gut syndrome, IBS, and even food allergies occur as much because of the individual as because of their gut biota. The studies regarding the variety of bacteria inhabiting different culture's intestines are providing phenomenal insights into some chronic disease progressions seen significantly in first world populations. This study is simply single faceted.

I'm not sure if it is the readers or the commenters, but when a study looks at high fat diet and the impact it has upon the physiology of the gut without considering the mouse obesity, you might realize the study is looking at physiologic changes of the gut - not changes in the gut biome, not changes in the percentage of body fat, but WHAT SPECIFIC DIETS DO TO MOUSE INTESTINAL CELLULAR FUNCTION. It MOST CERTAINLY IS NOT GARBAGE RESEARCH, but it isn't close to the whole picture.

It takes basic research like this correlated with the many other areas of ongoing research - hormonal triggers, gut biome diversity, comorbidity impact upon overall health, medications and supplements consumed - and yes, the blend of percentage fat in the body to lean body mass. This may not please two commenters, but in a few years time this study synthesized with other areas of research will yield meaningful results for humans. But we in medicine do know there is a gut/brain connection and are aware of the many trigger chemicals released by the alimentary system in response to food - not body mass, not balance of lean to muscle, etc. But thanks for the non-sequitors!