Scientists discovered that a special protein in your intestines called IL-22 plays an important role in controlling blood sugar levels and preventing weight gain. When researchers studied mice eating high-fat diets, they found that IL-22 helps produce another substance called GLP-1, which is famous for helping people manage diabetes and weight. The study shows that boosting IL-22 levels—even through eating certain foods that feed your gut bacteria—might help your body handle sugar better and stay healthier. This discovery could lead to new treatments for obesity and diabetes that work with your body’s natural systems.

The Quick Take

  • What they studied: Whether a gut protein called IL-22 helps control blood sugar and weight gain by triggering the production of GLP-1, a hormone that regulates insulin
  • Who participated: Male laboratory mice, some fed normal diets and others fed high-fat diets to mimic obesity and poor metabolic health
  • Key finding: Mice with higher IL-22 levels produced more GLP-1, had better blood sugar control, and maintained healthier insulin levels compared to mice with low IL-22. This effect worked through a specific cellular pathway called STAT3
  • What it means for you: This research suggests that maintaining healthy IL-22 levels in your gut—possibly through diet changes—might help your body control blood sugar naturally. However, this is early-stage research in mice, so human studies are needed before making health decisions

The Research Details

Researchers used laboratory mice to study how IL-22 affects blood sugar control during obesity. They created mice without IL-22 to see what happens when this protein is missing, then gave other mice extra IL-22 to see if it helped. They also tested whether butyrate (a substance produced when gut bacteria break down fiber) could increase IL-22 levels naturally. The team measured blood sugar, insulin levels, and pancreas health in all groups. They used molecular techniques to understand exactly how IL-22 works at the cellular level, discovering it activates a pathway called STAT3 that turns on the gene for GLP-1 production.

This research approach is important because it shows not just that IL-22 matters, but exactly how it works and what triggers it. By testing both removing IL-22 and adding it back, researchers could prove IL-22 is actually responsible for the effects. Testing butyrate is particularly valuable because it’s something humans can get from food, making the findings potentially practical for real-world use

This study was published in Nature Communications, a highly respected scientific journal, which suggests it passed rigorous peer review. The researchers used multiple approaches to confirm their findings—they tested mice without IL-22, mice given extra IL-22, and mice given butyrate. They also used molecular techniques to prove the exact mechanism. However, this is mouse research, so results may not directly apply to humans. The study focused only on male mice, so findings may differ in females

What the Results Show

When mice lacked IL-22, they produced less GLP-1 and had worse blood sugar control, even when eating normal food. When researchers gave these mice extra IL-22, their GLP-1 production increased, blood sugar control improved, and their pancreas returned to normal size. The effect was strong enough that giving IL-22 directly improved blood sugar tolerance in obese mice. Importantly, when researchers blocked GLP-1 with a special antagonist, IL-22 no longer helped—proving that IL-22 works specifically by triggering GLP-1 production. At the molecular level, IL-22 activated a protein called STAT3, which directly turned on the gene responsible for making GLP-1.

Butyrate supplementation—a substance produced when gut bacteria ferment fiber—increased IL-22 levels and improved GLP-1 production in mice. This effect only worked when IL-22 receptors were present, confirming that butyrate works through the IL-22 system. Mice treated with GLP-1 agonists (drugs that mimic GLP-1) recovered normal metabolic function even when IL-22 was low, showing that the benefits of IL-22 depend on GLP-1. Pancreatic islet size normalized with IL-22 treatment, suggesting the pancreas recovered from obesity-related damage

Previous research showed that IL-22 protects the intestinal barrier and that GLP-1 is crucial for blood sugar control and weight management. This study connects these two findings, showing that IL-22 doesn’t just protect the gut—it actively helps control metabolism. The discovery that butyrate (from fiber fermentation) increases IL-22 aligns with growing evidence that gut bacteria influence metabolic health. This research adds a new mechanism to explain why high-fiber diets and healthy gut bacteria are linked to better weight and blood sugar control

This research was conducted only in male mice, so results may differ in females or humans. The study doesn’t show whether these effects occur in humans or how long they last. Researchers used laboratory mice with controlled genetics and diets, which is very different from real human life with varied genetics, foods, and lifestyles. The study doesn’t test whether naturally increasing IL-22 through diet alone would produce the same benefits as direct IL-22 administration. Long-term safety of IL-22 treatment in humans hasn’t been established

The Bottom Line

Based on this research, maintaining a healthy gut microbiome through high-fiber foods may support IL-22 production and metabolic health (moderate confidence—mouse study only). Eating foods that promote butyrate production (whole grains, legumes, vegetables) is already recommended for general health and may have additional metabolic benefits. Do not attempt to self-treat obesity or diabetes based on this research—consult healthcare providers for proven treatments. This research suggests IL-22-based therapies could become future treatment options, but they’re not yet available or approved for human use

This research is most relevant to people with obesity, prediabetes, or type 2 diabetes who want to understand new treatment possibilities. It’s also important for researchers developing new metabolic therapies. People interested in how gut health affects overall metabolism should find this valuable. However, this is preliminary research, so it shouldn’t change current medical treatment decisions. Healthy individuals don’t need to make changes based on this single mouse study

In mice, IL-22 treatment improved blood sugar control relatively quickly, but the study doesn’t specify exact timeframes. If similar treatments are developed for humans, benefits would likely take weeks to months to become apparent, similar to other metabolic medications. Long-term effects and safety would need to be established through human clinical trials, which typically take several years

Want to Apply This Research?

  • Track daily fiber intake (target 25-35 grams) and weekly blood sugar readings if available, noting any patterns with high-fiber days. This helps users monitor whether dietary changes supporting gut health correlate with metabolic improvements
  • Gradually increase fiber intake through whole grains, legumes, vegetables, and fruits to support butyrate-producing gut bacteria. Start with one additional high-fiber food per day to avoid digestive discomfort, aiming for the recommended 25-35 grams daily
  • Weekly tracking of fiber intake, energy levels, and hunger patterns. Monthly check-ins with blood sugar readings if available. Note any changes in weight, digestion, or metabolic symptoms. Share data with healthcare providers to assess whether dietary changes are supporting metabolic health

This research was conducted in mice and has not been tested in humans. The findings do not yet support any medical treatments or dietary changes for obesity or diabetes. If you have diabetes, prediabetes, or obesity, consult your healthcare provider before making dietary changes or starting any new treatment. IL-22 therapies are not currently approved for human use. This article is for educational purposes only and should not replace professional medical advice. Do not attempt to self-diagnose or self-treat metabolic conditions based on this research.