Gut Microbiome Link Between High-Fat Diet and Heart Disease Identified

Gut Microbiome Link Between High-Fat Diet and Heart Disease Identified

Researchers at Vanderbilt University Medical Center and the University of California at Davis have identified what they think may be a link between consumption of a high fat diet and heart disease in a mouse model.

They believe that regular high-fat consumption may disrupt the gut microbiome and lead to the production of a harmful, disease-causing metabolite that can result in cardiovascular disease.

“Our research has revealed a previously unexplored mechanism for how diet and obesity can increase risk of cardiovascular disease — by affecting the relationship between our intestines and the microbes that live in our gut,” says Mariana Byndloss, assistant professor at Vanderbilt University Medical Center and co-lead author on the study, which is published in the journal Science.

Research has long suggested a link between high fat consumption and cardiovascular disease, but precise mechanisms have proved largely elusive. Recent studies have shown that high-fat consumption causes an imbalance in the gut microbiome, but again the exact reasons for this were unclear.

Byndloss and team investigated the impact of a high-fat diet on health and the gut microbiome in a mouse model. They found that such a diet causes inflammation and damages the cells lining the intestine, which in turn stops the mitochondria from working properly. This results in abnormal levels of oxygen and nitrate being produced by the intestinal cells.

This physiological change impacts the microbes living in the gut and encourages growth of bacteria such as Escherichia coli. This results in increased breakdown of choline, a dietary nutrient found mostly in meats and animal products such as eggs, into trimethylamine N-oxide (TMAO).

TMAO has been linked to atherosclerosis and other cardiovascular diseases, as well as all-cause mortality, in a number of studies published over the last 10 years and is thought to be pathogenic. While this study is only in mice and fairly early stage, it indicates that this bacterial metabolite could be a missing link between a high-fat diet and cardiovascular disease.

Mesalazine, also known as mesalamine or 5-aminosalicylic acid, is an approved drug used to treat inflammatory bowel disease. It functions by activating mitochondria in the intestinal cells. The researchers in this study found that treating the mice showing intestinal damage and high levels of TMAO in this study with this drug restored intestinal function and also stopped TMAO from increasing rapidly.

“This is evidence that it’s possible to prevent the negative outcomes associated with a high-fat diet,” Byndloss said.

“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.”

Byndloss and colleagues now plan to extend their studies and include animal models of cardiovascular disease in their work, as well as looking at the impact of the mechanisms of the gut microbiome on other diseases such as colorectal cancer.