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The IL23R gene encodes a receptor for IL-23, a cytokine that plays a role in gut inflammation. Read on to learn about the variants in this gene associated with inflammatory bowel disease—personalized tips included!
The IL23R gene encodes one part of the receptor for interleukin 23, a pro-inflammatory cytokine [R].
IL-23 activates Th17 cells, enabling them to release cytokines such as IL-17, IL-21, and IL-22. The primary purpose of this mechanism, known as the IL-23/Th17 axis, is to combat pathogens such as fungi and bacteria and prevent them from entering the body [R, R, R].
Additionally, IL-23 plays a role in the formation of new blood vessels or angiogenesis [R].
IL23R encodes one part of the receptor for IL-23, a pro-inflammatory cytokine that protects against fungi and bacteria.
Crohn’s disease (CD) and ulcerative colitis (UC) are two of the most frequently diagnosed subtypes of inflammatory bowel disease (IBD). The cause of IBD lies in a complex interplay of genetic and environmental factors [R].
Crohn’s mostly affects the small intestine and involves ulcerations of all cell layers of the gut lining. Ulcerative colitis typically affects the colon and rectum, and involves the inflammation of the gut mucosal layer [R, R].
Preclinical research has identified a crucial role of IL-23 in gut inflammation and different autoimmune conditions. Its activity peaks in the small intestine (terminal ileum) and colon, the most common IBD “targets” [R, R].
Animals with increased IL-23 expression have severe widespread inflammation, including the intestines [R].
Scientists have identified different SNPs in the IL23R gene associated with both Crohn’s disease and ulcerative colitis. Given their effects vary between populations, we will first outline the results for Europeans (Caucasians) and then mention the key differences in Asians.
A comprehensive review of 41 studies and over 47,000 participants has found a robust link between two SNPs and IBD [R]:
Combined, people with rs11209026-A had two times lower rates, and those with rs10889677-A had 37% higher rates of IBD.
In two meta-analyses of over 38,000 subjects, another IL23R variant correlated with ulcerative colitis. People with the “G” allele at rs7517847 had significantly lower UC rates. This allele was also protective against Crohn’s disease in a meta-analysis of 60 trials and 50K subjects [R, R, R].
When it comes to Asian populations [R, R, R, R]:
In European populations, people with rs11209026-A and rs7517847-G have lower chances, while those with rs10889677-A have higher chances of getting both Crohn’s disease and ulcerative colitis.
Given the critical role of IL-23 in gut inflammation, it’s no wonder that IL23R variants correlate with IBD. According to researchers, these SNPs can change the structure of IL-23 receptors, making them more or less responsive to stimulation [R, R].
Over-stimulation of IL23R increases IL-17 and triggers gut inflammation. Both CD and UC patients have elevated IL-17 in the gut lining [R, R, R]
While overactive IL-23 is harmful, the lack of it may also impair the gut microbiome. The exact mechanism behind IL23R variants in IBD is likely more complex and has yet to be unraveled [R, R, R].
The above SNPs can change the structure of IL-23 receptors, making them more or less responsive to stimulation. Its over-stimulation can trigger gut inflammation and contribute to IBD.
variant | genotype | frequency | risk allele |
rs11209026 | |||
rs10889677 | |||
rs7517847 |
Primary SNPs:
IL23R rs11209026
Population Frequency: Around 12% of European descendants carry the “A” allele. This allele is nearly non-existent in African and East-Asian populations.
IL23R rs10889677
Population Frequency: Around 50% of European descendants carry the “A” allele. It’s less common in East-Asian (46%) and African (24%) populations.
IL23R rs7517847
Population Frequency: Around 65% of Europeans and East-Asians carry at least one copy of the “G” allele. It’s less common among African descendants (30%).
FODMAPs are a group of carbohydrates identified as some of the prime irritants in IBD. FODMAPs is a catchy acronym that stands for Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols, such as [R, R, R]:
Specific oligosaccharides can increase the expression of IL-23 in the gut and thus worsen the impact of your variants [R].
Some experts recommend a low FODMAP diet to help control the symptoms of ulcerative colitis and Crohn’s disease. This diet isn’t appropriate for everyone—talk to your doctor or dietician to determine whether it could be right for you.
For more about the low FODMAP diet, check out this post on how it works and this post on which foods are included.
The low FODMAP diet eliminates specific foods that may increase IL-23 levels and trigger gut inflammation.
Omega-3 fatty acids found in fish, EPA and DHA, may inhibit Th17 cells and lower the levels of IL-17 and IL-23. High intake of fish and omega-3s may be protective against the development of Crohn’s disease [R, R, R, R].
A study of almost 200,000 women found that diets lower in potassium were associated with Crohn’s disease. The authors of the study suggested that dietary potassium could affect the Th17 pathway, which means it may counteract your genetic effect [R].
Crohn’s disease can also increase potassium secretion into the colon, potentially leading to deficiency [R].
Potassium-rich foods to help prevent deficiency include stone fruit (especially apricots and prunes), legumes, bananas, potatoes, and squash [R].
People with Crohn’s disease may be at higher risk of potassium deficiency. Potassium-rich foods may inhibit the Th17 pathway in gut inflammation.
Psychological stress has well-known detrimental effects on gut health and inflammation. It raises gut permeability and the levels of inflammatory Th17 cytokines, including IL-17 [R, R].
Many people with IBD develop anxiety and depression associated with their debilitating gastrointestinal symptoms. Furthermore, psychological stress may worsen the symptoms of IBD. Because of this potential feedback loop, many doctors emphasize the importance of managing the mental health of IBD patients [R, R, R, R].
Stress raises inflammatory cytokines such as IL-17 and worsens gut inflammation.
Andrographis paniculata, known as the “King of Bitters,” is traditionally used in Ayurveda and Chinese medicine. It may improve the symptoms of ulcerative colitis [R].
In two clinical trials, andrographolide, the active ingredient in Andrographis, improved UC by suppressing the IL-23/IL-17 axis [R, R].
Taking 1,200 – 1,800 mg Andrographis daily for 8 weeks reduced the symptoms of mild-to-moderate colitis in adults; the 1,800 mg dose was more effective. However, it did not affect remission rates any more than placebo [R].
Andrographis may help with ulcerative colitis by suppressing the IL-23/IL-17 axis.
In preclinical research, Lactobacillus and Bifidobacterium probiotic strains were able to reduce colon inflammation by blocking the IL-23/Th17 axis [R, R].
People with IBD often have impaired gut microbiome, which may worsen their disease. In a meta-analysis, a blended probiotic containing the above strains increased remission rates 1.7 times in ulcerative colitis patients [R].
These two strains generally appear to be beneficial in patients with ulcerative colitis [R, R, R, R].
Bifidobacterium and Lactobacillus probiotic strains may soothe colon inflammation by suppressing IL-23. They can be beneficial for ulcerative colitis patients.
Curcumin is the active ingredient of turmeric with potent anti-inflammatory effects. It can lower the levels of both IL-23 and IL-17 and thus lessen the impact of your IL23R gene [R, R, R].
Multiple clinical trials have produced promising results for curcumin in IBD, and further research is currently underway [R, R, R].
As mentioned, EPA and DHA from fish may lower the levels of IL-17 and IL-23. If you don’t eat at least two servings of fatty sea fish weakly, consider taking a fish oil supplement.
It is unclear whether omega-3 supplementation can help Crohn’s disease that has already developed and progressed. However, multiple studies have suggested that omega-3s may help keep it in remission [R, R].
Curcumin and fish oil inhibit IL-23 and IL-17. They can reduce gut inflammation and help keep IBD in remission.
Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.
Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.
The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.
Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.
Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.
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