Eating a Western diet impairs the immune system in the gut in ways that could increase risk of infection and inflammatory bowel disease, according to a study from the Washington University School of Medicine in St. Louis and Cleveland Clinic.
The study, in mice and people, showed that a diet high in sugar and fat causes damage to certain immune cells in the gut, called Paneth cells, that help keep inflammation in check. When Paneth cells aren't functioning properly, the gut immune system is excessively prone to inflammation, putting people at risk of inflammatory bowel disease and undermining effective control of disease-causing microbes.
The findings open up new approaches to regulating gut immunity by restoring normal Paneth cell function.
"Inflammatory bowel disease has historically been a problem primarily in Western countries such as the U.S., but it's becoming more common globally as more and more people adopt Western lifestyles," said the lead study author.
Paneth cell impairment is a key feature of inflammatory bowel disease. For example, people with Crohn's disease, a kind of inflammatory bowel disease characterized by abdominal pain, diarrhea, anemia and fatigue, often have Paneth cells that have stopped working.
Having high BMI associated with Paneth cell dysfunction
Researchers at Cleveland Clinic set out to find the cause of Paneth cell dysfunction in people. They analyzed a database containing demographic and clinical data on 400 people, including an assessment of each person's Paneth cells.
The researchers found that 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 his or her Paneth cells looked. The association held for healthy adults and people with Crohn's disease.
To better understand this connection, the researchers studied two strains of mice that are genetically predisposed to obesity. Such mice chronically overeat because they carry mutations that prevent them from feeling full even when fed a regular diet.
To the researchers' surprise, the obese mice had Paneth cells that looked normal.
High fat, high sugar diet the problem, not overweight
In people, obesity is frequently the result of eating a diet rich in fat and sugar. 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 chow, the mice had become obese and their Paneth cells looked decidedly abnormal.
"Obesity wasn't the problem per se," the lead author said. "Eating too much of a healthy diet didn't affect the Paneth cells. It was the high-fat, high-sugar diet that was the problem."
The Paneth cells returned to normal when the mice were put back on a healthy mouse diet for four weeks. Whether people who habitually eat a Western diet can improve their gut immunity by changing their diet remains to be seen.
"This was a short-term experiment, just eight weeks," Liu said. "It's possible that if you have Western diet for so long, you cross a point of no return and your Paneth cells don't recover even if you change your diet. We'd need to do more research before we can say whether this process is reversible in people."
The researchers are now investigating whether fat or sugar plays the primary role in impairing Paneth cells.
Source: Cell Host & Microbe, May 18, 2021
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