The Western Diet Can Damage These Immune Cells In The Gut

Eating a Western diet alters the gut immune system in a way that may increase the risk of infection and inflammatory bowel disease, new research in mice and humans indicates.

The study shows that a diet high in sugar and fat damages Paneth cells, the immune cells in the gut that help control inflammation.

When Paneth cells are not functioning properly, the intestinal immune system is excessively prone to inflammation, which puts people at risk for inflammatory bowel disease and compromises the effective control of pathogens.

The results, published in Cell host and microbe, open up new approaches to regulate intestinal immunity by restoring the normal function of Paneth cells.

“Inflammatory bowel disease has always been a problem primarily in Western countries like the United States, but it is becoming more and more common around the world as more people adopt Western lifestyles. Says lead author Ta-Chiang Liu, associate professor of pathology and immunology in Washington. University of Saint-Louis.

“Our research has shown that long-term consumption of a Western-style diet high in fat and sugar alters the function of immune cells in the gut in a way that promotes inflammatory bowel disease or increases the risk of ‘intestinal infections.’

Diet and damaged Paneth cells

Damage to Paneth cells is a key feature of inflammatory bowel disease. For example, in people with Crohn’s disease, a kind of inflammatory bowel disease characterized by abdominal pain, diarrhea, anemia, and fatigue, these cells have often stopped working.

“Obesity was not the problem in itself…. It was the high fat, high sugar diet that was the problem. “

Liu and lead author Thaddeus Stappenbeck – chairman of the Cleveland Clinic’s Department of Inflammation and Immunity and former co-director of the University of Washington’s laboratory and genomic medicine division – sought to find the cause. Paneth cell dysfunction in humans. They analyzed a database with demographic and clinical data on 400 people, including an assessment of each person’s Paneth cells.

Researchers found that a high body mass index (BMI) was associated with Paneth cells that looked abnormal and unhealthy under a microscope. The higher a person’s BMI, the worse their Paneth cells. The association was held for healthy adults and people with Crohn’s disease.

To better understand this link, the researchers studied two strains of mice genetically predisposed to obesity. These mice eat too often because they carry mutations that keep them from feeling full even when fed a regular diet. To the researchers’ surprise, the obese mice had Paneth cells that appeared normal.

In humans, obesity is often the result of a diet rich in fats and sugars. So the scientists fed normal mice a diet in which 40% of the calories came from fat or sugar, similar to the typical Western diet. After two months on this food, the mice had become obese and their Paneth cells appeared decidedly abnormal.

“Obesity was not the problem per se,” says Liu. “Eating too much of a healthy diet did not affect the Paneth cells. It was the high fat, high sugar diet that was the problem. “

Point of no return?

Paneth cells returned to normal when the mice were put on a healthy mouse diet for four weeks. Whether people who usually eat a Western diet can improve their gut immunity by changing their diet remains to be seen, Liu says.

“It was a short-term experience, barely eight weeks,” Liu said. “In humans, obesity doesn’t happen overnight or even in eight weeks… We would need to do more research before we can say whether this process is reversible in humans.

Further experiments have shown that a molecule known as deoxycholic acid, a secondary bile acid formed as a by-product of the metabolism of gut bacteria, forms the link between a Western diet and Paneth cell dysfunction. Bile acid increases the activity of two immune molecules – the farnesoid X receptor and type 1 interferon – which inhibit the function of Paneth cells.

Liu and his colleagues are currently studying whether fat or sugar plays the main role in the damage of Paneth cells. They also began to study ways to restore normal paneth cell function and improve gut immunity by targeting bile acid or both immune molecules.

The National Institutes of Health, the Helmsley Charitable Trust, the Genome Technology Access Center, and the University of Washington’s Digestive Disease Research Core Center funded the work.

Source: Washington University at St. Louis

About Hector Hedgepeth

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