Eating a Western Diet Impairs the Immune System in the Gut – May Increase Risk of Inflammation, Infection

Gut Organoids

A tiny, 3D model of the intestines formed from anti-inflammatory cells known as Paneth cells (green and red) and other intestinal cells (blue) is seen in the image above. Researchers at Washington University School of Medicine in St. Louis and the Cleveland Clinic used such models, called organoids, to understand why a Western-style diet rich in fat and sugar damages Paneth cells and disrupts the gut immune system. Credit: Ta-Chiang Liu

Diet rich in sugar, fat damages immune cells in digestive tracts of mice.

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 researchers at 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 Paneth cells, immune cells in the gut 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, published today (May 18, 2021) in Cell Host & Microbe, 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 lead author Ta-Chiang Liu, MD, PhD, an associate professor of pathology & immunology at Washington University. “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.”

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.

Liu and senior author Thaddeus Stappenbeck, MD, PhD, chair of the Department of Inflammation and Immunity 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.

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,” Liu 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, Liu said.

“This was a short-term experiment, just eight weeks,” Liu said. “In people, obesity doesn’t occur overnight or even in eight weeks. People have a suboptimal lifestyle for 20, 30 years before they become obese. 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.”

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.

Liu and colleagues 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.

Reference: “Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation” by Ta-Chiang Liu, Justin T. Kern, Umang Jain, Naomi M. Sonnek, Shanshan Xiong, Katherine F. Simpson, Kelli L. VanDussen, Emma S. Winkler, Talin Haritunians, Atika Malique, Qiuhe Lu, Yo Sasaki, Chad Storer, Michael S. Diamond, Richard D. Head, Dermot P.B. McGovern and Thaddeus S. Stappenbeck, 18 May 2021, Cell Host & Microbe.
DOI: 10.1016/j.chom.2021.04.004

Funding: National Institutes of Health, the Helmsley Charitable Trust, Washington University’s Genome Technology Access Center, Washington University’s Digestive Disease Research Core Center

18 Comments on "Eating a Western Diet Impairs the Immune System in the Gut – May Increase Risk of Inflammation, Infection"

  1. According to “science”, a western diet == high sugar and high fat.
    You learn something new every day…

  2. Headgoboomboom | May 18, 2021 at 7:02 pm | Reply

    Good, as then I don’t have to worry about the climate change that you usually dwell on!

  3. Trash study! Lumping fat and sugar together! Plenty of high fat foods are nutritionally dense and good for us such as eggs, whole milk, nuts, salmon, cheese, meat, etc. Only now do they say they will study fat and sugar separately after throwing this garbage out to the public first.

  4. Diet is key! We are what we eat, put in cooked but rotting flesh (meat) and animal pus/mucas (dairy & eggs), can’t be surprised when the body starts having severe issues!

    Constant meat and dairy consumption are NOT healthy for the human body and will always lead to health and digestive sooner, if not later.

  5. According to popular demand western diet is delicious and worth poor health globally is that what the conclusion was ?

  6. Brenda Joyce Knight | May 19, 2021 at 7:27 am | Reply

    Eating healthy products of vegetables and fruits into every day mealtime would make your gut gets fibers but you will still need your proteins like plants based products or fish,tuna,eggplant, things like that make you stronger. Water intake too.

  7. Sherrie Sperry | May 19, 2021 at 9:01 am | Reply

    Do you think we didn’t know this? This is all that is in stores. Growing up, our grocery stores were as big as CVS. That should tell you something.

  8. Educative

  9. Funny last two years I been using bathroom 8-10 times a day because of the way the food is made and processed in America. Wasted over 10,000k on food and it all went to waste.

    Just take the fat and sugar out the foods. Nobody cares for them and if they do who cares they will adapt I think everybody would rather be healthy and alive then sick and dead on inside

  10. You all that dumb? And obese too? Like the other 50% of Americans? Keep on deluding yourselves and enjoy the rest of your unhealthy existence. This article is right on. Your don’t need to know the science behind it all. You just need to get motivated to clean up your diet but it’s going to take some time, lots of discipline, and proper nutrition counseling which is very hard to find in America. I would suggest something called Functional Medicine as a good place to start. Pay good money for a professional consultation and plan. Then follow it to the T and you’ll get better quickly. You need to be very motivated because you will be changing your bad habits. It takes 6 weeks not a week less. That is 40 days–a magic number because that is how long it takes skin cells to regenerate and those little cells they’re talking about in this article are a type of skin cell. If you stop constantly poisoning yourself you can get your life back quickly. It cured my Crohn’s disease over a year ago.

  11. Funny, our scientists are always trying to tell the world how to eat. I think most societies are not listening, probably laughing and shaking their heads

  12. Butter is better | May 19, 2021 at 2:39 pm | Reply

    Define fat, please. Totally vague and misleading article. No doubt produced by the processed soy “meat” replacement people. There’s a huge difference between processed industrial polyunsaturated fats (aka “vegetable” oils) vs. well-sourced saturated fats (butter, ghee, coconut oil, lard, etc…) which are rich in vitamins A, D, and K2… essential nutrients deficient in the SAD Western diet.

  13. Michael Bender | May 19, 2021 at 3:00 pm | Reply

    Why does the URL say that it may damage the immune system, when the study showed that it does?

  14. I bet the issue is that our foods are over processed.

  15. I quit eating anything that has carbohydrates in a processed form, bread, rice, wheat, corn, potatoes…etc. I have almost obliterated all the aches and pains I had from my 20s and 40s. I feel better at 49 than I did at 21. The arthritis and inflammation was killing me. I eat meat and above ground vegetables and 90% of the time and it’s completely change my life.

  16. This is the exact program I followed to treat autoimmune disease naturally ( ). You’ll be absolutely thrilled with the step-by-step plan that guides you through the ultimate solution to treat the autoimmune disease, that you’ll only have one regret — and that is this: Not having had this valuable resource years ago!

  17. Duhhhh, like I didn’t know fat and sugar was bad for me. Waste of money on this tired research.

  18. Very vague and ridiculous article. What does it mean by western diet. What makes non western diet. Lot of diet south Asia is only carbs . Fat and sugar is the most general term.

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