High-fat diet disrupts biology of gut lining, promotes metabolite production

A high-fat diet disrupts the biology of the gut’s inner lining and its microbial communities, and promotes the production of a metabolite that may contribute to heart disease, according to a new study published in the journal Science. 

In previous studies, researchers have found that the epithelial cells lining the intestines and gut microbes share a mutually beneficial relationship that promotes a healthy gut environment. They wondered if diseases like obesity affect this relationship. 

For the current study, research teams found that a high-fat diet causes inflammation and damages intestinal epithelial cells in animal models. The high-fat diet impairs the function of energy-generating mitochondria, causing the intestinal cells to produce more oxygen and nitrate, the researchers said. These factors, in turn, stimulate the growth of harmful Enterobacteriaceae microbes, such as E. coli, and boost bacterial production of a metabolite called TMA (trimethylamine). The liver converts TMA to TMAO (trimethylamine-N-oxide), which has been implicated in promoting atherosclerosis and increasing the relative risk for all-cause mortality in patients. 

The discoveries in animal models support a key role for the intestines and microbiota in the development of cardiovascular disease, said Mariana Byndloss, DVM, PhD, assistant professor of Pathology, Microbiology, and Immunology at Vanderbilt University Medical Center. The intestines, she noted, have been relatively understudied by scientists seeking to understand the impact of obesity.

“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,” Byndloss said in a statement. “We show one way that diet directly affects the host and promotes the growth of bad microbes.”

Byndloss said she and her team plan to extend their studies into animal models of cardiovascular disease. They also are exploring the role of the host-microbe relationship in the development of other diseases, including colorectal cancer. 

“Our research has revealed a previously unexplored mechanism for how diet and obesity can increase risk of cardiovascular disease,” she said, “by affecting the relationship between our intestines and the microbes that live in our gut.”