High-fat diets rapidly deplete IL-22, weakening gut defenses and triggering silent inflammation. Unsaturated fats may help restore IL-22 and protect against chronic disease.
A study led by researchers at WEHI in Melbourne, Australia, is the first to reveal the immediate impact of a high-fat diet on gut health.
This pre-clinical research showed that just a few meals rich in saturated fats can trigger inflammation in the body, even though visible symptoms, such as those seen in chronic inflammation, may not appear for years.
These landmark findings highlight how quickly our diet can affect gut defenses and open the door for new strategies to strengthen gut health and combat chronic inflammation.
At a glance
- A landmark study has shown that the foods we eat each day can have an immediate impact on our gut health.
- Researchers found that the gut-protective protein IL-22 was significantly reduced in mice after only two days of consuming high-fat foods.
- The researchers hope these findings will guide future dietary recommendations aimed at naturally strengthening gut defenses and support the development of new approaches to restore or enhance gut function in people with chronic inflammatory diseases such as inflammatory bowel disease.
A silent threat to gut health
Around one in three Australians currently live with a chronic inflammatory condition, such as coeliac disease, inflammatory bowel disease, or rheumatoid arthritis.
However, the underlying causes of this inflammation and how it leads to disease are still not well understood.
Dr Cyril Seillet, a senior author on the paper, said the team’s findings were a significant breakthrough that could help pinpoint how chronic inflammation occurs at the source.
“We’ve shown that every meal we consume actively shapes our gut health,” Dr Seillet said.
“The more saturated fats we eat, the more inflammation that builds up – gradually weakening our gut defenses and increasing our susceptibility to chronic inflammation.
“But this inflammation build-up is initially silent, remaining hidden in our bodies until years later, where it can present as chronic inflammation.”
Researchers were able to detect microscopic changes to the gut health and function in mice even after a few high-fat meals, despite the mice lacking any visible symptoms of inflammation, such as weight gain.
“This shows how easily inflammation can develop without immediate warning signs,” Dr Seillet said.
“While occasional high-fat meals won’t impair your gut protection barrier, a consistent diet that is high in saturated fats is laying the foundation for chronic gut inflammation to present in future.”
Rapid immune response
In the study, with senior author and WEHI Laboratory Head Professor Stephen Nutt, researchers also found short-term exposure to high-fat diets can reduce the production of IL-22, a crucial protein that helps control gut inflammation.
It’s the first time the rapid impact of high fat diets on this protein has been shown.
First author on the paper, Le Xiong, said high-fat diets were a double hit to our gut barrier because they not only promoted inflammation, but also disabled the body’s ability to fight it.
“IL-22 is a critically important protein for gut health and protection. Without it, the gut loses its ability to prevent inflammation,” Le Xiong said.
“It took only two days of consuming high-fat foods for the mice to lose their IL-22 stores and have an impaired gut function.
“Despite their gut protection capabilities being stripped away, the mice still looked healthy – highlighting how gut health can be compromised long before any visible symptoms appear.”
The team observed that while saturated fats suppress IL-22 production, unsaturated fats, like those found in nuts and avocados, actually do the opposite and boost the protein’s production – a pattern researchers believe would be replicated in humans.
Therapeutic intervention potential
Researchers were able to rebuild the gut function of the mice in the study by restoring their IL-22 levels – highlighting the potential of creating a therapeutic intervention that can also restore gut health in humans.
But researchers want to first focus on ways to naturally boost IL-22 levels.
The team hopes their findings will influence dietary guidelines that emphasize the importance of incorporating unsaturated fats into our diets to naturally boost gut protection, while also promoting better nutrition-based strategies for people at risk of chronic inflammatory diseases.
Reference: “Acute exposure to high-fat diet impairs ILC3 functions and gut homeostasis” by Le Xiong, Shanti Diwakarla, Roxanne Chatzis, Olivia Artaiz, Matthew Macowan, Shengbo Zhang, Alexandra Garnham, Pooranee K. Morgan, Natalie A. Mellett, Peter J. Meikle, Graeme I. Lancaster, Benjamin J. Marsland, Stephen L. Nutt and Cyril Seillet, 14 April 2025, Immunity.
DOI: 10.1016/j.immuni.2025.03.017
This research is supported by the National Health and Medical Research Council (NHMRC) and involved collaborations with Monash University, the Baker Institute and the Department of Anatomy and Physiology at the University of Melbourne.
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1 Comment
And yet there is abundant evidence than low-carb/high-fat diets lead to substantial reduction in every available inflammatory marker such as uric acid, C-reactive protein, rheumatoid factor, anti-nuclear antigen, etc. Most importantly, this has been demonstrated over and over and over IN HUMANS, not mice.