Paneth cells, immune cells in the gastrointestinal epithelia, modulate innate immunity and infection. In Crohn’s disease, genetic mutations together with environmental triggers can disable the function of these cells. A team of researchers from the Washington University School of Medicine and the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute has found that a Western diet similarly leads to Paneth cell dysfunction. Their results appear in the journal Cell Host & Microbe.
“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 Dr. Ta-Chiang Liu, a researcher in the Department of Pathology and Immunology at the Washington University School of Medicine.
“Our research showed that long-term consumption of a Western-style diet high in fat and sugar impairs the function of immune cells in the gut in ways that could promote inflammatory bowel disease or increase the risk of intestinal infections.”
In the study, Dr. Liu and colleagues analyzed a database containing demographic and clinical data on 400 people, including an assessment of each person’s Paneth cells.
They 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, they 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 team’s surprise, the obese mice had Paneth cells that looked normal.
In people, obesity is frequently the result of eating a diet rich in fat and sugar. So the researchers 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.
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,” Dr. Liu said.
Further experiments showed that a molecule known as deoxycholic acid, a secondary bile acid formed as a byproduct of the metabolism of gut bacteria, forms the link between a Western diet and Paneth cell dysfunction.
The bile acid increases the activity of two immune molecules — farnesoid X receptor and type 1 interferon — that inhibit Paneth cell function.
The authors now are investigating whether fat or sugar plays the primary role in impairing Paneth cells.
They also have begun studying ways to restore normal Paneth cell function and improve gut immunity by targeting the bile acid or the two immune molecules.
Ta-Chiang Liu et al. Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation. Cell Host & Microbe, published online May 18, 2021; doi: 10.1016/j.chom.2021.04.004
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