Cholesterol in food causes inflammation in gut lining

Immune cells, coloured with fluorescent markers, in the gut of a zebrafish.

Scientists have discovered a possible way in which high fat diets might lead to inflammation in the gut.

Working with mice and zebrafish, researchers at Imperial College London discovered that cholesterol, a component of fatty foods, triggers an inflammatory response in the cells lining the gut and impairs the movement of food through the gut.

Some patients with inflammatory bowel disease report that eating fatty food can worsen their symptoms, although this has not been confirmed in studies. The new findings, published in Nature Communications, could explain how this effect might occur.

Professor Maggie Dallman, from the Department of Life Sciences at Imperial, who led the study, said: “In humans, inflammation in the gut is associated with a number of conditions that cause pain and discomfort, such as irritable bowel syndrome. The relationship between these conditions and diet is poorly understood, so we were interested in exploring how fatty diets might cause inflammation.

“We studied zebrafish because they have similar immune systems to mammals, and their guts have a similar architecture. They are also translucent, which makes it easy to study what’s happening inside their bodies. We also studied mice to confirm that the effects are similar in mammals.”

The researchers found that feeding the animals cream or butter caused acute inflammation in the gut lining.

They then showed that this was directly caused by cholesterol binding to a protein found on the epithelial cells that line the gut. The response was also dependent on signals from particular microbes that live in the gut.

After 10 days on a high cholesterol diet, the waves of muscle contraction and relaxation that push food through the intestine were impaired. In humans, this effect is a common symptom of gastro-intestinal disorders, such as irritable bowel syndrome.

Study author Fränze Progatzky, also from the Department of Life Sciences at Imperial, said: “What’s surprising about our findings is that the initial response to cholesterol occurs not in immune cells, but in the cells of the gut lining. We plan to research these effects further and investigate their possible role in human disease.”

The research was funded by the Biotechnology and Biological Sciences Research Council, the Wellcome Trust, and the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).  

Reference: F. Progatzky et al. ‘Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation.’ Nature Communications, 2014. DOI: 10.1038/ncomms6864