Small intestine inflammation causes major problems in the gut. It negatively affects nutrient digestion and absorption while creating nasty symptoms including:

• Gas & bloating
• Cramping
• Diarrhea
• Intestinal permeability
• Impaired mucosal immunity
• Gut dysbiosis
• Loss of appetite
• Weight loss

Last week’s blog covered how stress induces Crohn’s disease flare ups. The basic jist is that chronic stress causes elevation of glucocorticoids(cortisol). As a result, immune cells that make an important cytokine called IL-22 become depleted. You can check that blog out here.

IL-22 is an incredibly important cytokine for maintaining gut health. When we look at everything it does, we see that it’s a major player in balancing the gut.

It also weaves together several important concepts that we know make a healthy gut. Factors such as:

• Circadian rhythms
• Carbohydrate & fat digestion and absorption
• Intestinal permeability
• Intestinal repair
• Balance in the microbiome
• FUT2 status

In today’s blog we’ll touch on these things and discuss how IL-22 may be how carbohydrate restriction improves gut health for some people.

Small intestine inflammation, homeostasis, and IL-22

Health of the small intestine plays an important role in our health and quality of life. When we eat, a healthy small intestine helps us break down and absorb the nutrients in our food.

Additionally, our small intestine has to be ready for insults that come with our food. This includes bacteria, fungi, environmental toxins, and things of that nature.

IL-22 seems to help balance these functions to help maintain homeostasis. Immune cells in the gut known as type 3 innate lymphoid cells(ILC3) produce IL-22 in a circadian manner. As far as circadian rhythms go, you’re not going to get a more robust rhythms than this:

ILC3 cells are critically important for maintaining homeostasis throughout the gut. Their secretion of IL-22 helps promote a strong barrier and healthy microbiome free of pathogens.

But when we eat, specifically fat or carbohydrate, there’s an inhibition of IL-22. With carbohydrate, gamma delta T cells block IL-22 secretion. This alters the program in our gut from protection against pathogens to enhancement of digestion and absorption.

As a result, inhibiting IL-22 increases digestive enzyme production and nutrient transport. On the other hand, increased IL-22 inhibits these digestive processes and initiates an antimicrobial program.

Consequently, this circadian and feeding driven pattern prevents small intestine inflammation and helps maintain balance. Interestingly, IL-22 also helps repair damage by promoting intestinal epithelial cell repair, and regulates the microbiome through antimicrobial peptide secretion.

IL-22: There’s an upside and a downside

As is everything in biology, IL-22 is very complex. If IL-22 is too low, we lack protection against pathogens. If it’s too high, we’ll have problems properly digesting and absorbing our food.

As you can see, there’s and upside and a downside…

In the normal, healthy gut, periods of high and low IL-22 driven by environmental signals keep things healthy. But with chronic inflammation, we can have either chronically low or high IL-22.

As is generally the case with things that follow a circadian rhythm, we want a period of high expression and a period of low expression. Most importantly, creating and maintaining a rhythm of IL-22 prevents “leaky gut” by:

• Promoting epithelial cell renewal
• Improving the mucus layer by increasing FUT2 expression
• Keeping pathogens low via antimicrobial peptide secretion
• Controlling inflammation

You can check the many beneficial effects of IL-22 in preventing small intestine inflammation in a review found here. On the other hand, this pic from the paper summarizes it nicely:

Carb restriction, IL-22, and gut health

Could the relationship between carbohydrate consumption and IL-22 explain why low carbohydrate diets seem to help some people with gut problems? It seems plausible.

Clearly, IL-22 is really important for maintaining a healthy small intestine. But we don’t want it chronically high or chronically low, we want a healthy rhythm. A healthy rhythm creates gut health through many mechanisms as seen below:

For some individuals, this rhythm may get jacked up. And while carbohydrates inhibit IL-22, polyphenols and fiber actually active it.

In mice, skewing the diet from high carbohydrate to high protein reprograms the gut with respect to IL-22 by remodeling the small intestine. Consequently, we may be able to use a short-term low carb/high protein diet to re-establish equilibrium by reprogram our gut.

After that, reintroduction of the right foods at the right time over time may attain balance. Most importantly, healthy circadian habits are critical to creating this robust IL-22 rhythm.

The circadian clock is essential for ILC3 cells in the gut, and inflamed tissue from IBD patients shows circadian disruption in ILC3 cells. Strong circadian rhythms driven by regular behavior are essential to homeostasis in the gut

Conclusion

Controlling small intestine inflammation is necessary to maintaining a healthy gut. The cytokine IL-22 is a central player in maintaining the balance between preventing infection and nutrient digestion and absorption.

Therefore, it’s important to prioritize behaviors that establish the proper circadian rhythm of IL-22. This helps promote homeostasis in the small intestine.

However, certain individuals may have dysregulated IL-22 signaling due to pre-existing damage, infection, or microbial dysbiosis. As a result, dietary factors such as carbohydrate, fiber, and polyphenols may cause more problems than they solve.

In these individuals, addressing behaviors that regulate circadian rhythms while changing diet by reducing carbohydrate, polyphenols, and fiber may re-establish the IL-22 rhythm. After a short period of restriction, reintroduction can re-stabilize the gut and make it more resilient to dietary insults.