167 | id == 167
167 | category_id == 16
167 | category_order == 13
167 | category_name == Gut Health
167 | category_color == #C47AC0
167 | slug == TLR4-IBD
167 | title == A Genetic Link Between Antibacterial Response & IBD (TLR4)
167 | meta_description == TLR4 is an inflammation activator that communicates closely with the gut flora. What role does it play in IBD? Learn more here.
167 | summary == <p><strong>TLR4 is an inflammation activator that communicates closely with the gut flora and helps identify good vs. bad bacteria. What role does it play in IBD? Read on to learn more.</strong></p>
167 | overall_score_text == Gut Inflammation Score (based on TLR4)
167 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/TLR4--Gut-Inflammation-IBD---all-chips.jpg
167 | author_id == 1
167 | author_name == Jasmine Foster
167 | author_title == BSc, BEd
167 | author_order == 36
167 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
167 | 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>
167 | reviewer == None
167 | medical_reviewer_id == 11
167 | medical_reviewer_name == Puya Yazdi
167 | medical_reviewer_title == MD
167 | publish_date == 2020
167 | publish_date == 5
167 | publish_date == 1
167 | avg_rating == 5.0
167 | tags_id == 195
167 | tags_name == Crohn's Disease
167 | tags_id == 308
167 | tags_name == Gut Inflammation
167 | tags_id == 73
167 | tags_name == IBD
167 | tags_id == 387
167 | tags_name == TLR4 Gene
167 | tags_id == 386
167 | tags_name == Toll-Like Receptors
167 | permissions_favorite == False
167 | permissions_rate == False
167 | 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. Keep in mind that these results are based on association studies, which are correlative and aren&rsquo;t necessarily causative. In addition, any one 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. Furthermore, a variant associated with one ethnicity doesn&rsquo;t necessarily apply to other ethnicities. Therefore, just because you have one of these genotypes does not necessarily mean you are at increased risk of developing this condition!</span></em></p> <h2><span style="font-weight: 400;">What is TLR4?</span></h2> <p><span style="font-weight: 400;">TLR4 codes for toll-like receptor 4. This protein jump-starts the innate immune response, which is a mechanism our bodies have for fighting pathogens we have never encountered before [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748601/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">TLR4 recognizes foreign compounds on the surface of invading pathogens (usually bacteria) and activates the immune response. As part of this process, it increases 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 cytokines like </span><a href="http://selfhacked.com/blog/interleukin-1/"><span style="font-weight: 400;">IL-1</span></a><span style="font-weight: 400;"> and </span><a href="https://www.selfdecode.com/gene/IL12a/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">IL-12</span></a><span style="font-weight: 400;"> [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25581309"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25071777"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</span></p> <h3><span style="font-weight: 400;">TLR4 in the Gut</span></h3> <p><span style="font-weight: 400;">TLR4 is believed to interact with many aspects of gut function and metabolism. It is itself regulated by the presence of nutrients; certain saturated fatty acids produced by </span><a href="https://www.selfhacked.com/blog/gut-bacteria-microbiome/"><span style="font-weight: 400;">gut bacteria</span></a><span style="font-weight: 400;"> activate it, while more complex, unsaturated fatty acids block it [</span><a href="https://academic.oup.com/edrv/article/36/3/245/2354681"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">TLR4 is a proinflammatory signal, meaning that when it is active, it promotes inflammation. Some researchers believe that it is a central player in the chronic, low-grade inflammation present in obesity [</span><a href="https://academic.oup.com/edrv/article/36/3/245/2354681"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">TLR4 &amp; the Gut Flora</span></h3> <p><span style="font-weight: 400;">Recent research suggests that the gut flora can actively regulate TLR4; some signals from the gut bacteria suppress it, while others activate it [</span><a href="https://www.hindawi.com/journals/jir/2014/586939/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686520/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">For example, </span><a href="http://selfhacked.com/blog/health-benefits-butyrate-derivatives-sodium-butyrate-phenylbutyrate-trybutyrine-butyric-acid-butyrate-prodrugs-butyrate-producing-bacteria/"><span style="font-weight: 400;">butyrate</span></a><span style="font-weight: 400;">, typically considered highly beneficial, actually increases the expression of TLR4. However, total </span><a href="https://selfhacked.com/blog/lipopolysaccharides/"><span style="font-weight: 400;">lipopolysaccharides</span></a><span style="font-weight: 400;"> (</span><a href="https://www.selfhacked.com/blog/lipopolysaccharides/"><span style="font-weight: 400;">LPS</span></a><span style="font-weight: 400;">) - normally considered harmful - produced by the human gut flora block TLR4 activation [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126326/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some researchers have suggested that this communication between the gut flora and TLR4 is essential for the human body to be able to tolerate all those bacteria in our intestines&mdash;but also to respond to harmful bacteria. If TLR4 is not properly regulated, it may trigger inflammatory reactions to harmless bacteria, throw off the balance of the intestinal ecosystem, and promote disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686520/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.hindawi.com/journals/jir/2014/586939/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225216/"><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;">TLR4 is an immune-regulating receptor that promotes the inflammatory response. It communicates closely with the gut flora, helping the body tolerate good bacteria and identify threats.</span></p> <h2><span style="font-weight: 400;">TLR4 Variants &amp; IBD</span></h2> <p><span style="font-weight: 400;">One TLR4 variant, rs4986791, has been associated both with Crohn&rsquo;s disease and with disease severity in young patients with IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824893/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30423580"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">At this SNP, the rare &lsquo;T&rsquo; allele was associated with childhood IBD severity in a Danish study and with Crohn&rsquo;s disease in a Malaysian study. In both studies, people with the &lsquo;TT&rsquo; genotype were more susceptible to disease than people with the &lsquo;CC&rsquo; genotype. However, the Malaysian study found that people with the &lsquo;CT&rsquo; genotype were the most likely to have Crohn&rsquo;s disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824893/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30423580"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;T&rsquo; allele of rs4986791 has been linked to a variety of other inflammatory conditions, including diabetes, rheumatoid arthritis, Alzheimer&rsquo;s disease, and heart disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824893/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Because TLR4 promotes the inflammatory response, the &lsquo;T&rsquo; allele of rs4986791 is believed to increase TLR4 activation [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824893/"><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;">The &lsquo;T&rsquo; allele of rs4986791 is associated with Crohn&rsquo;s disease, increased severity of childhood IBD, and possibly increased TLR4 activation.</span></p> <h2><span style="font-weight: 400;">Your TLR4 Results for IBD</span></h2> <p>*9285838631582455*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>TLR4 rs4986791</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = No association with Crohn&rsquo;s disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with Crohn&rsquo;s disease and with IBD severity in Malaysian and Danish studies</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;CT&rsquo; = Strongly associated with Crohn&rsquo;s disease in a Malaysian study</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only about 8% of all people worldwide have at least one copy of the &lsquo;T&rsquo; allele.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;T&rsquo; allele is significantly more common in people of South Asian (22%) descent and essentially nonexistent in people of East Asian (0%) descent.</span></li> </ul> <p>*9339764520327742*</p> <h2><span style="font-weight: 400;">Recommendations to Reduce Inflammation</span></h2> <p>*8221054516431447*</p> <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> <h3><span style="font-weight: 400;">Lifestyle</span></h3> <h4><span style="font-weight: 400;">Exercise</span></h4> <p><a href="https://selfhacked.com/blog/top-14-proven-health-benefits-exercise-references-mechanisms/"><span style="font-weight: 400;">Exercise</span></a><span style="font-weight: 400;"> has been found to reduce TLR4 expression in humans and animals. Moderate exercise may be more beneficial for this purpose than short bursts of high-intensity exercise, which may produce more inflammation [</span><a href="https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-017-0111-2"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Broadly speaking, exercise may have a mild protective effect on the development of IBD; that is, people who are already physically active are somewhat less likely to develop Crohn&rsquo;s than those who are sedentary [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743119/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some people with severe IBD may not be able to exercise as strenuously as healthy peers. However, if the intensity of exercise is limited, then physical activity is believed to be beneficial for IBD patients. Physically fit people have less inflammation, a healthier immune response, lower weight, better mental health, and stronger bones [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743119/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660805/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022156/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">If you have IBD, we recommend talking to your doctor about how much physical activity would be beneficial in your case.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Exercise may reduce TLR4 expression. If you have IBD, moderate exercise may be beneficial, but be careful not to overexert yourself.</span></p> <h4><span style="font-weight: 400;">Sun Exposure</span></h4> <p><span style="font-weight: 400;">In a clinical trial on 44 obese people, supplementation with </span><a href="http://selfhacked.com/blog/35proven-health-benefits-vitamin-d-part-1/"><span style="font-weight: 400;">vitamin D</span></a><span style="font-weight: 400;"> decreased blood TLR4 levels [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30246883"><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 (and the steroids used to treat it) have been linked to </span><a href="https://selfhacked.com/blog/calcium-101/"><span style="font-weight: 400;">calcium</span></a><span style="font-weight: 400;"> and vitamin D deficiencies and subsequent osteoporosis. Your doctor will monitor your vulnerability to these deficiencies, and if appropriate, prescribe supplements [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16112594"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257592/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757415/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><a href="https://selfhacked.com/blog/avoiding-sun-will-kill-14-proven-science-based-health-benefits-sun/"><span style="font-weight: 400;">Sun exposure</span></a><span style="font-weight: 400;"> is one of the main ways that the body obtains vitamin D. If your doctor does not advise you to take supplements, you can get enough vitamin D from under an hour of sun [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129901/"><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;">Vitamin D deficiency is a risk during IBD treatment. If your doctor does not recommend supplements, sun exposure is the best way to get vitamin D.</span></p> <h3><span style="font-weight: 400;">Diet</span></h3> <h4><span style="font-weight: 400;">Vitamin A Sufficiency</span></h4> <p><a href="http://selfhacked.com/blog/importance-real-vitamin-retinol/"><span style="font-weight: 400;">Vitamin A</span></a><span style="font-weight: 400;"> plays a central role in healthy communication between TLR4 and the gut flora [</span><a href="https://www.frontiersin.org/articles/10.3389/fmicb.2019.00268/full"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Deficiency of vitamin A is somewhat common in IBD patients. Your doctor will monitor your vitamin and mineral levels and recommend supplements if necessary; otherwise, make sure to include vitamin A rich foods (like liver, sweet potato, spinach, and carrots) in your diet [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342481/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Broccoli Sprouts (Sulforaphane)</span></h4> <p><span style="font-weight: 400;">Cruciferous vegetables, which include broccoli, kale, brussels sprouts, and other related plants, are rich in a compound called </span><a href="http://selfhacked.com/blog/panacea-benefits-broccoli-sprouts-sulforaphane/"><span style="font-weight: 400;">sulforaphane</span></a><span style="font-weight: 400;"> which has been found to block TLR4 [</span><a href="https://www.hindawi.com/journals/iji/2018/2859135/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Sulforaphane has also been found to reduce gut inflammation and improve colitis symptoms in mice [</span><a href="http://www.jimmunol.org/content/192/8/3530.long"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24231100"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Sulforaphane-rich cruciferous vegetables are often cited as anti-inflammatory foods and recommended as part of a healthy diet. However, many sources warn against cruciferous vegetables for patients with IBD [</span><a href="https://clinphytoscience.springeropen.com/articles/10.1186/s40816-015-0011-2"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770165/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021001/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some people with IBD may tolerate cruciferous vegetables better than others. These vegetables contain insoluble fibers that fall into the category of FODMAPs, which may be dietary triggers for some [</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;">Sulforaphane is also available as a supplement for those who want to try it but avoid food sources.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Sulforaphane blocks TLR4 and may reduce gut inflammation, but cruciferous vegetables may be dietary triggers for some. Work with a doctor or nutritionist to determine whether they are safe for you.</span></p> <h4><span style="font-weight: 400;">Tea</span></h4> <p><a href="http://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">Green tea</span></a><span style="font-weight: 400;"> is rich in catechins, including </span><a href="https://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">EGCG</span></a><span style="font-weight: 400;">. In cell studies, EGCG decreased the expression of TLR4. In animals, EGCG also reduces many of the inflammatory markers associated with IBD. Some researchers have therefore suggested that green tea should be recommended to IBD patients; human trials are currently lacking [</span><a href="https://www.future-science.com/doi/full/10.4155/fmc-2017-0172"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490540/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Omega-3 Fatty Acids</span></h4> <p><span style="font-weight: 400;">Omega-3 fatty acids are healthy fats and among the unsaturated fats believed to block the activation of TLR4. Many nutritionists strongly recommend seeking out dietary sources, including fish and nuts [</span><a href="https://academic.oup.com/edrv/article/36/3/245/2354681"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://ods.od.nih.gov/factsheets/Omega3FattyAcids-Consumer/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a clinical trial of 49 obese pregnant women, supplementation with omega-3 fatty acids (</span><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;"> and EPA) reduced the expression of TLR4 in body fat and the placenta. These fatty acids also lowered TLR4 levels in cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560373/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In one study, 4.2 grams of </span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">fish oil</span></a><span style="font-weight: 400;"> daily for 8 months reduced the symptoms of active mild-to-moderate ulcerative colitis [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/1553930"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, a review of three clinical trials and 138 ulcerative colitis patients found no significant benefits of fish oil supplementation. The authors suggested further trials with improved fish oil formulation (enteric-coated capsules) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17636844"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">An increased ratio of omega-3 fats to omega-6 fats is associated with reduced inflammation and reduced rates of IBD, including ulcerative colitis. The more omega-3 and the less omega-6 fatty acids people consumed the less likely they appeared to be to develop IBD. It is currently unclear whether omega-3 supplementation could help with existing cases of ulcerative colitis [</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;">Omega-3 fatty acids decrease TLR4 expression and are often recommended to IBD patients as healthy dietary fats.</span></p> <h3><span style="font-weight: 400;">Supplements</span></h3> <h4><span style="font-weight: 400;">Curcumin</span></h4> <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 popular anti-inflammatory compound that comes from turmeric. In mouse and cell studies, this compound blocked TLR4 and improved the symptoms of TLR4-induced gut inflammation [</span><a href="https://www.hindawi.com/journals/iji/2018/2859135/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In one small study, curcumin reduced the frequency of bowel movements, diarrhea, and stomach pain in people with Crohn&rsquo;s disease after a month of daily supplementation [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16240238?dopt=Abstract"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">At least two clinical studies so far have found a possible benefit for curcumin supplementation in ulcerative colitis, either alone or in combination with conventional medications. Remember to never combine supplements with medications without first discussing these combinations with your doctor [</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;">Curcumin, a popular anti-inflammatory supplement, blocks TLR4 and may reduce gut inflammation in Crohn&rsquo;s disease.</span></p> <h4><span style="font-weight: 400;">NAC</span></h4> <p><span style="font-weight: 400;">In animal studies, </span><a href="http://selfhacked.com/blog/top-25-science-based-health-benefits-n-acetyl-cysteine-nac/"><span style="font-weight: 400;">NAC</span></a><span style="font-weight: 400;"> reduced TLR4 expression as part of its anti-inflammatory effect [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28485782"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22532030"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">NAC also reduced gut inflammation In 37 people with colitis, helping to reduce inflammatory substances like </span><a href="http://selfhacked.com/blog/il-8/"><span style="font-weight: 400;">IL-8</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18473409"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In rats, NAC supplementation strengthened the intestinal barrier and boosted antioxidant defense [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17305994"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Probiotics</span></h4> <p><span style="font-weight: 400;">Certain </span><a href="https://selfhacked.com/blog/probiotics-good-bacteria/"><span style="font-weight: 400;">probiotic</span></a><span style="font-weight: 400;"> strains reduced TLR4 activation in animal studies. In rats with gut inflammation, a blend of </span><a href="http://selfhacked.com/blog/b-longum/"><em><span style="font-weight: 400;">B. longum</span></em></a><span style="font-weight: 400;">, </span><a href="http://selfhacked.com/blog/l-delbrueckii/"><em><span style="font-weight: 400;">L. bulgaricus</span></em></a><span style="font-weight: 400;">, and </span><a href="http://selfhacked.com/blog/s-thermophilus/"><em><span style="font-weight: 400;">S. thermophilus</span></em></a><span style="font-weight: 400;"> decreased inflammation while blocking TLR4.</span><em><span style="font-weight: 400;"> L. jensenii</span></em><span style="font-weight: 400;"> had a similar effect in pigs [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364977/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890654/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><a href="https://selfhacked.com/blog/probiotics-good-bacteria/"><span style="font-weight: 400;">Probiotics</span></a><span style="font-weight: 400;"> work by changing the composition of the gut flora, adding in beneficial species. As such, many strains are under investigation for their potential to improve gut disorders like IBD.</span></p> <p><span style="font-weight: 400;">Some types of human gut bacteria, particularly </span><em><span style="font-weight: 400;">Bacteroides</span></em><span style="font-weight: 400;"> and </span><em><span style="font-weight: 400;">Prevotella</span></em><span style="font-weight: 400;"> species, produce compounds that suppress TLR4 signalling [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686520/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A meta-analysis of a blended </span><a href="https://selfhacked.com/blog/probiotics-gut-health/"><span style="font-weight: 400;">probiotic</span></a><span style="font-weight: 400;"> containing </span><a href="https://selfhacked.com/blog/b-longum/"><em><span style="font-weight: 400;">Bifidobacteria</span></em></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/l-plantarum/"><em><span style="font-weight: 400;">Lactobacillus</span></em></a><span style="font-weight: 400;">, and </span><em><span style="font-weight: 400;">Streptococcus </span></em><span style="font-weight: 400;">species (VSL#3) found that remission rates rose by 1.7x in ulcerative colitis patients taking the probiotic compared to the placebo [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24280877"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In animal models of IBD, the probiotic species that have produced positive results include </span><a href="https://selfhacked.com/blog/health-benefits-l-plantarum/"><em><span style="font-weight: 400;">L. plantarum</span></em></a><span style="font-weight: 400;">, </span><a href="http://selfhacked.com/blog/b-bifidum/"><em><span style="font-weight: 400;">B. bifidum</span></em></a><span style="font-weight: 400;">, and </span><a href="http://selfhacked.com/blog/s-boulardii/"><em><span style="font-weight: 400;">S. boulardii</span></em></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21996541"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222668/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17218154"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17087945"><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;">TLR4 has a close relationship with gut bacteria, and some probiotics may reduce TLR4 activation and improve the symptoms of IBD.</span></p> <h4><span style="font-weight: 400;">Ginseng</span></h4> <p><span style="font-weight: 400;">Some of the active compounds of </span><a href="https://selfhacked.com/blog/ginseng/"><span style="font-weight: 400;">ginseng</span></a><span style="font-weight: 400;"> appear to reduce the production of cytokines by decreasing TLR4 expression [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437451/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In animals, fermented wild ginseng reduced the severity of colitis, cytokine expression, and inflammation. In cell studies, the same fermented product reduced the production of inflammatory cytokines [</span><a href="https://www.sciencedirect.com/science/article/pii/S122684531830157X"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Skullcap</span></h4> <p><span style="font-weight: 400;">In cell studies, an active compound from skullcap called </span><a href="http://selfhacked.com/blog/baicalein-baicalin-top-7-health-benefits-flavanoid/"><span style="font-weight: 400;">baicalin</span></a><span style="font-weight: 400;"> decreased inflammation by reducing the expression of TLR4 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025220/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Human studies are lacking, but in animal studies, skullcap extracts reduced the severity of colitis and decreased intestinal permeability [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923812/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/abs/pii/S0308814613000666"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Cordyceps</span></h4> <p><span style="font-weight: 400;">In a clinical trial of 98 people with chronic kidney disease, supplementation with </span><a href="https://selfhacked.com/blog/introduction-to-cordyceps/"><em><span style="font-weight: 400;">Cordyceps</span></em></a> <span style="font-weight: 400;">lowered the levels of TLR4 and other inflammatory markers. Its active compound cordycepin had similar effects in cells by directly blocking TLR4 signaling [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462325/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a mouse study, </span><em><span style="font-weight: 400;">Cordyceps sinensis</span></em><span style="font-weight: 400;"> extract reduced the symptoms of colitis, including </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;">, diarrhea, and bleeding. These effects have not been investigated in humans [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270544/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694364/"><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;">Other anti-inflammatory supplements that may block TLR4 and reduce gut inflammation include ginseng, skullcap, and cordyceps. Human studies are lacking for these possible effects.</span></p>
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167 | content_learn_more_9339764520327742_text == Based on the variants we looked at, your TLR4 gene is associated with slightly increased rates and severity of IBD (Crohn’s disease). However, this doesn't necessarily reflect your overall risk of IBD, just one gene related to it. Physical fitness, a healthy diet, and anti-inflammatory supplements may help; read on to learn more.
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