174 | id == 174
174 | category_id == 16
174 | category_order == 13
174 | category_name == Gut Health
174 | category_color == #C47AC0
174 | slug == TLR9-crohns-IBS
174 | title == A DNA-Binding Immune Receptor’s Link to Crohn’s Disease & IBS (TLR9)
174 | meta_description == Toll-like receptor 9 (TLR9) senses bacterial and viral DNA and activates the immune response. What happens when it goes wrong?
174 | summary == <p><strong>Toll-like receptor 9 (TLR9) senses bacterial and viral DNA and activates the immune response. But what happens when something goes wrong and it reacts to human DNA? Read on to learn more.</strong></p>
174 | overall_score_text == Gut Inflammation Score (based on TLR9)
174 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/TLR9--Gut-Crohns---all-chips.jpg
174 | author_id == 1
174 | author_name == Jasmine Foster
174 | author_title == BSc, BEd
174 | author_order == 36
174 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
174 | author_intro == <p><strong>Jasmine received her BS from McGill University and her BEd from Vancouver Island University.</strong></p>    <p>Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.</p>
174 | reviewer == None
174 | medical_reviewer_id == 11
174 | medical_reviewer_name == Puya Yazdi
174 | medical_reviewer_title == MD
174 | publish_date == 2020
174 | publish_date == 5
174 | publish_date == 4
174 | avg_rating == 5.0
174 | tags_id == 195
174 | tags_name == Crohn's Disease
174 | tags_id == 194
174 | tags_name == Gut Health
174 | tags_id == 308
174 | tags_name == Gut Inflammation
174 | tags_id == 73
174 | tags_name == IBD
174 | tags_id == 8
174 | tags_name == IBS
174 | tags_id == 410
174 | tags_name == TLR9 Gene
174 | tags_id == 386
174 | tags_name == Toll-Like Receptors
174 | permissions_favorite == False
174 | permissions_rate == False
174 | content_article == <p><em><span style="font-weight: 400;">This article is for informational purposes only. None of the information here should be taken as medical advice. If you suspect you may have digestive issues, seek medical help. </span></em><em><span style="font-weight: 400;">Keep in mind that these results are based on association studies, which are correlative and aren&rsquo;t necessarily causative. Any single genetic variant will typically contribute only a small proportion to the overall risk of the condition, and non-genetic factors play a large role in developing a condition as well. Therefore, just because you have one of these genotypes does not necessarily mean you are at an increased risk of developing this condition!</span></em></p> <h2><span style="font-weight: 400;">What is TLR9?</span></h2> <p><em><span style="font-weight: 400;">TLR9</span></em><span style="font-weight: 400;"> codes for toll-like receptor 9, one of a family of toll-like receptors which also includes </span><a href="../article/tlr4-ibd-167"><span style="font-weight: 400;">TLR4</span></a><span style="font-weight: 400;">. TLR9 senses the presence of bacterial or viral DNA and triggers an immune response to protect the body from invading pathogens [</span><a href="https://www.ncbi.nlm.nih.gov/gene/54106"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041324/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21947771"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30623441"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Most of the time, when TLR9 is working correctly, it specifically targets DNA belonging to potentially dangerous invaders. However, excessive activation of TLR9 may result in human DNA being targeted, which in turn may lead to an autoimmune response [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041324/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708030/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h2><span style="font-weight: 400;">TLR9 in the Gut</span></h2> <p><span style="font-weight: 400;">In the digestive system, TLR9 plays an important role in protecting against changes in the gut flora and metabolism. Mice with very low TLR9 expression also have much more difficulty healing intestinal wounds [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28094890"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://onlinelibrary.wiley.com/doi/full/10.1002/oby.21215"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, because TLR9 sends inflammatory signals, too much can cause problems. TLR9 activation increases the production of </span><a href="http://selfhacked.com/blog/supplements-people-th1-dominant/"><span style="font-weight: 400;">Th1</span></a><a href="http://selfhacked.com/blog/th17/"><span style="font-weight: 400;">7</span></a><span style="font-weight: 400;"> cells and cytokines, which can lead to chronic inflammation and autoimmunity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708030/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30891627"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">One potential outcome of this autoimmune response is the development of inflammatory diseases like IBS or Crohn&rsquo;s disease.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">TLR9 differentiates between beneficial and potentially harmful bacteria in the gut and activates the immune response if there is a threat.</span></p> <h3><span style="font-weight: 400;">What is Crohn&rsquo;s Disease?</span></h3> <p><span style="font-weight: 400;">IBD is a group of autoimmune diseases characterized by inflammation and sores in the gut lining, which can result in diarrhea, abdominal </span><a href="https://selfhacked.com/blog/23-ways-to-combat-pain-naturally-by-increasing-your-opioids/"><span style="font-weight: 400;">pain</span></a><span style="font-weight: 400;">, fatigue, fever, rectal bleeding, nutritional deficiencies, and </span><a href="http://selfhacked.com/blog/a-comprehensive-list-of-effective-ways-to-lose-weight/"><span style="font-weight: 400;">weight loss</span></a><span style="font-weight: 400;">. The definition of IBD includes both ulcerative colitis and Crohn&rsquo;s disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980998/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Crohn&rsquo;s disease differs from ulcerative colitis in that it is centered higher in the digestive tract (typically in the small intestine, though it can occur anywhere between the mouth and anus) and may damage broader swaths of tissue [</span><a href="https://www.niddk.nih.gov/health-information/digestive-diseases/ulcerative-colitis"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.niddk.nih.gov/health-information/digestive-diseases/crohns-disease/definition-facts"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">What is IBS?</span></h3> <p><span style="font-weight: 400;">Irritable bowel syndrome (IBS) is a gut condition that causes abdominal pain, bloating, and dysregulated bowel movements. The NIH estimates that as many as 20% of Americans may experience signs of IBS, but doctors still don&rsquo;t know the exact causes behind this syndrome [</span><a href="https://en.wikipedia.org/wiki/Linaclotide"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">There are two main types of IBS: one that involves diarrhea (IBS-D) and one that involves constipation (IBS-C).</span></p> <h3><span style="font-weight: 400;">The Role of TLRs in Gut Inflammation</span></h3> <p><span style="font-weight: 400;">Because of their ability to activate the immune and inflammatory responses, toll-like receptors are under intense investigation as central players in the development of IBS &amp; IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/abs/pii/S1043661817310605"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">TLRs sense and regulate the beneficial bacteria that live in our guts and differentiate them from harmful invaders. When they sense a potential threat, they trigger a cascade of inflammation through </span><a href="https://selfhacked.com/blog/nuclear-factor-kappa-b/"><span style="font-weight: 400;">NF-&kappa;B</span></a><span style="font-weight: 400;"> and T cell activation. TLRs are, in turn, suppressed by </span><a href="http://selfhacked.com/blog/treg/"><span style="font-weight: 400;">Tregs</span></a><span style="font-weight: 400;">, a type of </span><a href="https://selfhacked.com/blog/how-to-increase-and-decrease-white-blood-cells/"><span style="font-weight: 400;">white blood cell</span></a><span style="font-weight: 400;"> that restrains and calms the immune system [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">People with IBS &amp; IBD tend to have too much inflammation and not enough Tregs, suggesting a potential imbalance of TLRs [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">What About TLR9?</span></h3> <p><span style="font-weight: 400;">Researchers disagree about the precise role of TLR9 in Crohn&rsquo;s disease and other inflammatory diseases of the gut. Some studies seem to suggest that it is protective; however, genetic studies have found lower rates of IBD in people with lower TLR9 expression. Furthermore, a study of IBD patients found increased TLR9 expression linked to increased disease severity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074037/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Despite the disagreements, most of the evidence suggests that high TLR9 is linked to worse IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074037/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">If TLR9 is activated when there is no bacterial threat, it may cause harmful inflammation. Many studies have linked excessive TLR9 to Crohn&rsquo;s disease and other inflammatory diseases.</span></p> <h2><span style="font-weight: 400;">TLR9 Variants &amp; Gut Inflammation</span></h2> <h3><span style="font-weight: 400;">Crohn&rsquo;s Disease</span></h3> <p><span style="font-weight: 400;">Multiple studies have found potential links between TLR9 genetic variants and Crohn&rsquo;s disease. The most significant associations have been in three SNPs: rs352139, rs352140, and rs574383 [</span><a href="https://www.gastrojournal.org/article/S0016-5085(04)00982-5/fulltext"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20044998"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://link.springer.com/article/10.1007/s12026-018-9061-0"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Of these, rs352139 has been studied the most. Researchers have produced differing results when associating this SNP with IBD, but the &lsquo;T&rsquo; allele is generally considered protective. The &lsquo;T&rsquo; allele also decreases expression of TLR9, supporting the idea that excess TLR9 may contribute to IBD [</span><a href="https://www.gastrojournal.org/article/S0016-5085(04)00982-5/fulltext"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074037/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Other SNPs that have been linked with Crohn&rsquo;s disease include rs5743836-G and rs352140-T, though these have not been studied as well, and they are also not available on most commercial DNA chips [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20044998"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://link.springer.com/article/10.1007/s12026-018-9061-0"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19455129"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">IBS</span></h3> <p><span style="font-weight: 400;">Some studies have also found links between TLR9 variants and IBS, a less severe disorder likewise caused by gut inflammation. Generally speaking, the same alleles associated with IBD are also associated with IBS [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20044998"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773304/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><em><span style="font-weight: 400;">TLR9 </span></em><span style="font-weight: 400;">variants that increase expression, such as rs352139-T, have been associated with increased rates and severity of Crohn&rsquo;s disease and IBS.</span></span></p> <h2><span style="font-weight: 400;">Your TLR9 Results for Gut Inflammation</span></h2> <p>*6414250614597088*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>TLR9 rs352139</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Relatively higher TLR9 expression, not protective against IBD or IBS</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Relatively lower TLR9 expression, protective against IBD &amp; IBS</span></li> </ul> <p><strong>TLR9 rs352140</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Not associated with IBD &amp; IBS</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with IBD &amp; IBS</span></li> </ul> <p><strong>TLR9 rs5743836</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Not associated with IBD &amp; IBS</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with IBD &amp; IBS, even in the presence of protective variants in other genes (IL23R &amp; NOD2)</span></li> </ul> <p>*9515122917524346*</p> <h2><span style="font-weight: 400;">Recommendations to Reduce Gut Inflammation</span></h2> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*8947382444096093*</p> <h3><span style="font-weight: 400;">Stress Management</span></h3> <p><span style="font-weight: 400;">Chronic </span><a href="https://selfhacked.com/blog/63-factors-raising-stress-cortisol-level-backed-science/"><span style="font-weight: 400;">stress</span></a><span style="font-weight: 400;"> is believed to activate TLR9, contributing to inflammation and long-term detrimental effects on the immune system [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401452/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27793667"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Many people with IBD develop </span><a href="https://selfhacked.com/blog/natural-treatments-anxiety/"><span style="font-weight: 400;">anxiety</span></a><span style="font-weight: 400;"> and </span><a href="https://selfhacked.com/blog/natural-treatments-depression/"><span style="font-weight: 400;">depression</span></a><span style="font-weight: 400;"> associated with their debilitating gastrointestinal symptoms. Furthermore, psychological stress is broadly believed to worsen symptoms of IBD. Because of this potential feedback loop, many doctors emphasize the importance of managing the mental health of IBD patients [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774724/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28245757"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678997/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572298/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">If you have clinical symptoms of anxiety or depression, your doctor may refer you to a psychologist for further evaluation and treatment. Regardless, you may want to try other stress-busting activities like </span><a href="https://selfhacked.com/blog/health-benefits-yoga/"><span style="font-weight: 400;">yoga</span></a><span style="font-weight: 400;"> or </span><a href="https://selfhacked.com/blog/meditation/"><span style="font-weight: 400;">meditation</span></a><span style="font-weight: 400;">, provided that they don&rsquo;t interfere with your doctor&rsquo;s treatment plan.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Chronic stress is linked to both increased TLR9 and IBD. Stress management strategies, including psychological treatment, are often recommended to IBD patients.</span></p> <h3><span style="font-weight: 400;">Fish &amp; Fish Oil</span></h3> <p><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">DHA</span></a><span style="font-weight: 400;"> is a type of omega-3 fatty acid primarily found in fish and fish oil. It is generally considered an anti-inflammatory fat, and it may reduce TLR9 activity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916003/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Omega-3 fatty acid intake, including from fish, has been inversely linked to the development of Crohn&rsquo;s disease; that is, people who eat more fish (and omega-3s) appear less likely to get Crohn&rsquo;s [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153885/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">It is unclear whether DHA supplementation can help Crohn&rsquo;s disease that has already developed and progressed. However, multiple studies have suggested that omega-3 fatty acids (including DHA)&nbsp; may help keep Crohn&rsquo;s disease in remission [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153885/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700845/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Curcumin</span></h3> <p><a href="https://selfhacked.com/blog/curcumin-cures-top-15-scientifically-proven-health-benefits-with-references/"><span style="font-weight: 400;">Curcumin</span></a><span style="font-weight: 400;"> is a natural anti-inflammatory compound extracted from turmeric. Multiple studies have found that it decreases the expression of many toll-like receptor genes, including TLR9 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30623441"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/pii/S2211383515001379"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22138522"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Multiple clinical trials have produced promising results for curcumin in IBD (including Crohn&rsquo;s), and further research is currently underway. Remember to never combine supplements with medications without first discussing these combinations with your doctor [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29957091"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514688/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153885/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Some natural anti-inflammatory compounds may reduce TLR9 activity. These include DHA, an omega-3 fatty acid found in fish oil, and curcumin, a popular supplement.</span></p>
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174 | content_learn_more_9515122917524346_text == Based on the variants we looked at, your TLR9 gene is associated with roughly average rates of Crohn’s disease. However, this doesn't necessarily reflect your overall risk of Crohn’s disease, just one gene related to it. Stress management strategies, fish oil, and curcumin may help; keep reading to learn more.
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rsIDs = rs574383,rs5743836,rs352139,rs352140
rsStatus = rs574383,LOC105369519,chr11,118702959,T,C,,,20,15,HET
rsStatus = rs5743836,TLR9,chr3,52226766,A,G,,,34,0,Normal
rsStatus = rs352139,TLR9,chr3,52224356,T,A,C,G,28,0,Normal
rsStatus = rs352140,TLR9,chr3,52222681,C,A,G,T,32,0,Normal
