182 | id == 182
182 | category_id == 16
182 | category_order == 13
182 | category_name == Gut Health
182 | category_color == #C47AC0
182 | slug == TNFSF15-IBD
182 | title == Can Your Variants of This Gene Protect You From Inflammatory Bowel Disease? (TNFSF15)
182 | meta_description == TNFSF15 amplifies the immune response and may contribute to gut inflammation. Learn where your variants stand here.
182 | summary == <p style="text-align:justify"><strong>The TNFSF15 gene encodes a protein that amplifies the effects of inflammatory cytokines. Its activity may also worsen gut inflammation in people with IBD. Read below to learn more about this gene and whether your variants may contribute to gut inflammation.</strong></p>
182 | overall_score_text == IBD Score (based on TNFSF15 gene)
182 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/TNFSF15--Gut-Inflammation-IBD---all-chips.jpg
182 | author_id == 12
182 | author_name == Carlos Tello
182 | author_title == PhD
182 | author_order == 55
182 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
182 | author_intro == <p><strong>Carlos received his PhD and MS from the Universidad de Sevilla.</strong></p>    <p>Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.</p>
182 | author_social_media_name == linkedin
182 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
182 | author_social_order == 1
182 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
182 | reviewer == None
182 | medical_reviewer_id == 11
182 | medical_reviewer_name == Puya Yazdi
182 | medical_reviewer_title == MD
182 | publish_date == 2020
182 | publish_date == 5
182 | publish_date == 11
182 | avg_rating == 5.0
182 | tags_id == 195
182 | tags_name == Crohn's Disease
182 | tags_id == 96
182 | tags_name == Cytokines
182 | tags_id == 308
182 | tags_name == Gut Inflammation
182 | tags_id == 73
182 | tags_name == IBD
182 | tags_id == 428
182 | tags_name == TNFSF15 Gene
182 | tags_id == 196
182 | tags_name == Ulcerative Colitis
182 | tags_id == 341
182 | tags_name == Zinc
182 | permissions_favorite == False
182 | permissions_rate == False
182 | 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 immediately. </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. In addition, 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 increased risk of developing this condition!</span></em></p> <h2><strong>What Is the <em>TNFSF15 </em>Gene?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../gene/tnfsf15/"><em><span style="font-weight: 400;">TNFSF15 </span></em><span style="font-weight: 400;">gene</span></a><span style="font-weight: 400;"> encodes a cytokine from the tumor necrosis factor (</span><a href="../article/tnf-longevity-86"><span style="font-weight: 400;">TNF</span></a><span style="font-weight: 400;">) family</span> <span style="font-weight: 400;">called &lsquo;</span><em><span style="font-weight: 400;">TNF superfamily member 15</span></em><span style="font-weight: 400;"> (TNFSF15)&rsquo;. The protein is also commonly known as TL1A (&lsquo;</span><em><span style="font-weight: 400;">Tumor necrosis factor-like cytokine 1A</span></em><span style="font-weight: 400;">&rsquo;) and VEGI (&lsquo;</span><em><span style="font-weight: 400;">Vascular endothelial growth inhibitor</span></em><span style="font-weight: 400;">&rsquo;) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14568967/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763597/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">TNFSF15 is expressed at very low levels by tissue lining cells and inactive immune cells. Upon recognizing inflammatory cytokines, antibodies, and foreign microbes, immune cells such as T cells, macrophages, and dendritic cells increase their production of this protein [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11911831/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17371957/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373837/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760084/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">TNFSF15 exerts its function by binding to DR3 (&lsquo;</span><em><span style="font-weight: 400;">Death receptor 3</span></em><span style="font-weight: 400;">&rsquo;), a protein mainly produced by activated T cells, B cells, and </span><a href="http://selfhacked.com/blog/intro-natural-killer-cells-increase-decrease/"><span style="font-weight: 400;">natural killer cells</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15760679/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15153521/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614993/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15814728/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">By enhancing the effects of the cytokines that stimulate these processes, the TNFSF15/DR3 interaction promotes the proliferation, maturation, and function of the following immune cells:</span></p> <ul> <li style="font-weight: 400;"><a href="http://selfhacked.com/blog/supplements-people-th1-dominant/"><span style="font-weight: 400;">Th1</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11911831/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14568967/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="http://selfhacked.com/blog/supplements-people-th2-dominant/"><span style="font-weight: 400;">Th2</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053556/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19406102/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Th9 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/31176785"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112176/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="http://selfhacked.com/blog/th17/"><span style="font-weight: 400;">Th17</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373838/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="http://selfhacked.com/blog/treg/"><span style="font-weight: 400;">Tregs</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947231/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053556/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/intro-natural-killer-cells-increase-decrease/"><span style="font-weight: 400;">NK cells</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15153521/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900590/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">As a result, TNFSF15 helps fight off infections by amplifying the immune response. Unfortunately, its excessive or uncontrolled activation is associated with inflammatory and autoimmune diseases such as IBD, rheumatoid arthritis, ankylosing spondylitis, and primary biliary cirrhosis [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880748/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763597/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>What Is Inflammatory Bowel Disease?</strong></h3> <p><span style="font-weight: 400;">Inflammatory bowel disease (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;"> [</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><a href="https://selfhacked.com/blog/crohns-disease/"><span style="font-weight: 400;">Crohn&rsquo;s disease</span></a><span style="font-weight: 400;"> and </span><a href="https://selfhacked.com/blog/ibd-ulcerative-colitis-crohn-genetics-lifestyle-stress-infections/"><span style="font-weight: 400;">ulcerative colitis</span></a><span style="font-weight: 400;"> are the most frequently diagnosed subtypes of IBD. Both conditions share some features but differ in the regions affected:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Crohn's may affect any portion of the gastrointestinal tract, but mostly the ileum (lower part of the small intestine). It involves ulcerations of all cell layers of the gut lining [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622286/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Ulcerative colitis typically affects the colon and rectum. It causes the inflammation of the mucosal layer (innermost cell layer) of the gut [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30837080"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> </ul> <p><span style="font-weight: 400;">The cause of IBD lies in a complex interplay of </span><a href="https://selfhacked.com/blog/ibd-ulcerative-colitis-crohn-genetics-lifestyle-stress-infections/"><span style="font-weight: 400;">genetic and environmental factors</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106026/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>Role of TNFSF15 in Gut Function and Inflammation</strong></h3> <p><span style="font-weight: 400;">The TNFSF15/DR3 pathway promotes the development of T cells in the gut lining to produce inflammatory cytokines that help fight off bacterial and viral infections [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22259035/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016081/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460213/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Importantly, the pathway activates a group of immune cells that promote mucosal immunity and barrier function (innate lymphoid cells) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998636/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301104/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595159/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">These studies support a role of TNFSF15 in sustaining gut lining function in normal conditions and during acute infections. However, its excessive activation seems to contribute to IBD and chronic gut inflammation.</span></p> <p><span style="font-weight: 400;">IBD is associated with an increased production of both TNFSF15 and DR3. Higher levels of these proteins were measured in intestinal macrophages, dendritic cells, and T cells from people with Crohn&rsquo;s disease, and in B cells from those with ulcerative colitis. In the case of Crohn&rsquo;s, TNFSF15 levels were highest in the most severe cases [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19834969/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648040/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14568967/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15207783/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Studies in mice show that TNFSF15 sustains bowel inflammation and tissue scarring by activating the Th1 and Th17 responses, resulting in an increased production of pro-inflammatory cytokines such as </span><a href="http://selfhacked.com/blog/interleukin-1/"><span style="font-weight: 400;">IL-1</span></a><a href="http://www.selfdecode.com/gene/IL13/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">3</span></a><span style="font-weight: 400;">, IL-17A, and </span><a href="https://www.selfhacked.com/blog/interferon-gamma-how-to-increase-decrease-high-low-levels/"><span style="font-weight: 400;">IFN-&gamma;</span></a><span style="font-weight: 400;"> in the gut lining [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437258/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053556/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019214/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19834969"><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;"><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">TNFSF15 </span></em><span style="font-weight: 400;">gene encodes a cytokine that amplifies the immune response. This normally helps fight off infections but can worsen IBD and other inflammatory conditions.</span></span></p> <h2><strong><em>TNFSF15 </em>Variants and Inflammatory Bowel Disease</strong></h2> <h3><strong>Protective Variants</strong></h3> <p><span style="font-weight: 400;">Four </span><em><span style="font-weight: 400;">TNFSF15 </span></em><span style="font-weight: 400;">polymorphisms have been most widely studied:</span></p> <ul> <li style="font-weight: 400;"><a href="../../snp/rs3810936/"><span style="font-weight: 400;">rs3810936</span></a><span style="font-weight: 400;">: located in the region of the gene that encodes the protein (</span><em><span style="font-weight: 400;">exon</span></em><span style="font-weight: 400;">), it doesn&rsquo;t change the sequence of amino acids but may modify its shape. Its major allele &lsquo;C&rsquo; is associated with higher TNFSF15 levels and activity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211638/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30488533"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><a href="../../snp/rs6478108/"><span style="font-weight: 400;">rs6478108</span></a><span style="font-weight: 400;">: its major variant &lsquo;T&rsquo; is associated with increased TNFSF15 levels and activity in macrophages, colon cancer cells, and gut lining of people with IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169936/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584785/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22684480"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><a href="../../snp/rs6478109/"><span style="font-weight: 400;">rs6478109</span></a><span style="font-weight: 400;">: located in the region that controls gene expression (</span><em><span style="font-weight: 400;">promoter</span></em><span style="font-weight: 400;">). Its minor variant &lsquo;A&rsquo; has been associated with higher TNFSF15 levels in immune cells, but &lsquo;G&rsquo; increased them in the gut lining of people with IBD and colon cancer cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130856/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979016/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22684480"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584785/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><a href="../../snp/rs7848647/"><span style="font-weight: 400;">rs7848647</span></a><span style="font-weight: 400;">: its minor variant &lsquo;T&rsquo; was associated with lower blood TNFSF15 levels in people with rheumatoid arthritis, while &lsquo;C&rsquo; increased the levels of this protein in the gut lining of people with IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30488533"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22684480"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> </ul> <p><span style="font-weight: 400;">The minor variants at these polymorphisms protected from IBD (especially Crohn&rsquo;s disease) in several studies of British, European, Japanese, Korean, Chinese, and Indian adults, as well as in Korean Children [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18338776"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16221758/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19174806"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856432/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20367632"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23850713"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25731871/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979016/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18422820"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929548/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264777/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25998826"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In contrast, the major &lsquo;G&rsquo; allele of rs7848647 was associated with an early age of Crohn&rsquo;s diagnosis (under 16 years old) in an American study [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25664710"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">The minor allele &lsquo;A&rsquo; of </span><a href="../../snp/rs4263839/"><span style="font-weight: 400;">rs4263839</span></a><span style="font-weight: 400;">, associated with reduced protein levels in the blood and gut lining, protected against Crohn&rsquo;s and ulcerative colitis in 3 studies on Indian, Chinese, and Italian populations. However, this variant was also associated with an increased progression of the disease in a Slovenian study [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264777/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29996264"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144927/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29446656"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">The minor &lsquo;C&rsquo; allele at </span><a href="../../snp/rs7869487/"><span style="font-weight: 400;">rs7869487</span></a><span style="font-weight: 400;"> was protective against Crohn&rsquo;s disease in 3 studies on British, European, and Indian populations, and against both Crohn&rsquo;s and ulcerative colitis in Japanese [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18338776"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19174806"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264777/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16221758/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Inheriting several of the major variants together has been associated with higher levels of the TNFSF15 protein and more severe IBD symptoms in different populations [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552994/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648040/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19174806"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28624054"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>Risk Variants</strong></h3> <p><span style="font-weight: 400;">Two cases of minor TNFSF15 variants conferring increased susceptibility to Crohn&rsquo;s disease have been identified:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;T&rsquo; variant of </span><a href="../../snp/rs4979462/"><span style="font-weight: 400;">rs4979462</span></a><span style="font-weight: 400;"> (in Japanese and Korean populations). It increases </span><em><span style="font-weight: 400;">TNFSF15 </span></em><span style="font-weight: 400;">expression by promoting the binding of a protein that activates it [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16221758/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856432/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979016/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25899471"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;T&rsquo; variant of </span><a href="../../snp/rs6478106/"><span style="font-weight: 400;">rs6478106</span></a><span style="font-weight: 400;"> (in Chinese and Japanese populations) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23266558/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929548/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> </ul> <h3><strong>Disease Outcomes</strong></h3> <p><span style="font-weight: 400;">The protective variant at rs6478108 was, however, associated with Crohn&rsquo;s complications such as narrowings and fistulas in a Korean study [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24835165"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor variants of </span><a href="../../snp/rs11554257/"><span style="font-weight: 400;">rs11554257</span></a><span style="font-weight: 400;"> and </span><a href="../../snp/rs2006996/"><span style="font-weight: 400;">rs2093403</span></a><span style="font-weight: 400;"> were associated with increased severity of ulcerative colitis and need for the surgical removal of the colon [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959149/"><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;">TNFSF15 </span></em><span style="font-weight: 400;">variants that lower the expression of the gene are associated with a reduced incidence of IBD, especially Crohn&rsquo;s disease, while those that increase it confer susceptibility.</span></span></p> <h2><strong>Your <em>TNFSF15 </em>Results for Inflammatory Bowel Disease</strong></h2> <p>*2984402296885080*</p> <p>&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP: </strong><strong><em>TNFSF15 </em></strong><strong>rs3810936</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Reduced risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> </ul> <p><strong>Other Important SNPs:&nbsp;</strong></p> <p><strong><em>TNFSF15 </em></strong><strong>rs6478108</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Reduced risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Normal risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> </ul> <p><strong><em>TNFSF15 </em></strong><strong>rs6478109</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Reduced risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> </ul> <p><strong><em>TNFSF15 </em></strong><strong>rs7848647</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Reduced risk of Crohn&rsquo;s disease.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of Crohn&rsquo;s disease. Associated with early age of diagnosis.</span></li> </ul> <p><strong><em>TNFSF15 </em></strong><strong>rs4263839</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Reduced risk of Crohn&rsquo;s disease and ulcerative colitis. Associated with disease progression and need for surgery.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> </ul> <p><strong><em>TNFSF15 </em></strong><strong>rs7869487&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Reduced risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Normal risk of Crohn&rsquo;s disease and ulcerative colitis.</span></li> </ul> <p><strong><em>TNFSF15 </em></strong><strong>rs4979462&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of Crohn&rsquo;s disease.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased risk of Crohn&rsquo;s disease.</span></li> </ul> <p><strong><em>TNFSF15 </em></strong><strong>rs6478106&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of Crohn&rsquo;s disease.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased risk of Crohn&rsquo;s disease.</span></li> </ul> <h4><strong>Population Frequency</strong></h4> <p><span style="font-weight: 400;">The distribution of all protective polymorphisms (rs3810936, rs6478108, rs6478109, rs7848647, rs4263839, and rs7869487) is very similar. Approximately 55% of the world population carries two copies of each major allele. The minor allele is most common in people with East Asian ancestry (~76% carriers of at least one copy) and especially rare in African descendants (only 1% carry two copies).&nbsp;</span></p> <p><span style="font-weight: 400;">The risk allele &lsquo;T&rsquo; of rs4979462 is most common among people with an African background (~60% carriers of at least one copy) and rarest in European descendants (only 0.2% carry two copies).</span></p> <p><span style="font-weight: 400;">The genotypes of the rs6478106 polymorphism are similarly distributed among the different ethnicities. Approximately 43% of the world population carries two copies of the major allele &lsquo;C&rsquo; versus only 13% homozygous for &lsquo;T&rsquo;.</span></p> <p>*3730983979068858*</p> <p>&nbsp;</p> <h2><strong>Strategies that May Improve Your Inflammatory Bowel Disease</strong></h2> <p>*4272382708621367*</p> <p>&nbsp;</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><strong>Diet</strong></h3> <h4><strong>Low-FODMAP Diet</strong></h4> <p><span style="font-weight: 400;">FODMAPs are a group of carbohydrates identified as some of the prime irritants in IBD. FODMAPs is a catchy acronym that stands for </span><span style="font-weight: 400;">F</span><span style="font-weight: 400;">ermentable </span><span style="font-weight: 400;">O</span><span style="font-weight: 400;">ligosaccharides, </span><span style="font-weight: 400;">D</span><span style="font-weight: 400;">isaccharides, </span><span style="font-weight: 400;">M</span><span style="font-weight: 400;">onosaccharides, </span><span style="font-weight: 400;">A</span><span style="font-weight: 400;">nd </span><span style="font-weight: 400;">P</span><span style="font-weight: 400;">olyols, such as [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28244679"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">,</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843040/"> <span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">,</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388522/"> <span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Fructose</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Lactose</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Fructans and galactans</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Galacto-oligosaccharides</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Polyols (sugar alcohols)</span></li> </ul> <p><span style="font-weight: 400;">Some experts recommend a low-FODMAP diet to help control the symptoms of ulcerative colitis and Crohn&rsquo;s disease.</span></p> <p><span style="font-weight: 400;">Specific oligosaccharides can increase the expression of </span><a href="https://www.selfdecode.com/gene/il23r/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">IL-23</span></a><span style="font-weight: 400;"> in the gut. This may worsen IBD, especially in people with overactive </span><em><span style="font-weight: 400;">TNFSF15 </span></em><span style="font-weight: 400;">variants that amplify IL-23 effects [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743503/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19834969"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In addition, some of these FODMAPs enhanced the Th1 and Th17 immune responses in animal and cell-based studies [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17920536"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15550119"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101117/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239808/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808656/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">For more about the low-FODMAP diet, check out</span><a href="https://selfhacked.com/blog/fodmap-diet/"> <span style="font-weight: 400;">this post</span></a><span style="font-weight: 400;"> on how it works and</span><a href="https://selfhacked.com/blog/fodmap-food-list/"> <span style="font-weight: 400;">this post</span></a><span style="font-weight: 400;"> on which foods are included.</span></p> <h4><strong>Resistant Starch and Butyrate</strong></h4> <p><span style="font-weight: 400;">IBD may cause alterations in the </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;"> that result in lower production of </span><a href="http://selfhacked.com/blog/health-benefits-butyrate-derivatives-sodium-butyrate-phenylbutyrate-trybutyrine-butyric-acid-butyrate-prodrugs-butyrate-producing-bacteria/"><em><span style="font-weight: 400;">butyrate</span></em></a><span style="font-weight: 400;">, a short-chain fatty acid that preserves the ability of the gut lining to take up nutrients while blocking the absorption of microbes and their toxic products [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/31498864"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636678/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Butyrate may reduce inflammation by increasing the activity of immune cells called regulatory T cells or Tregs. These specialized cells stop other immune cells &ndash; Th1, Th2, and Th17 &ndash; in their tracks, before they lose control. In turn, Tregs prevent the lining of the gut from overreacting to harmless food proteins [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24226770"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Butyrate also reduced TNFSF15 levels in human cells isolated from the inner lining of the lung arteries but increased them in cells from small blood vessels. The specific effects of butyrate on TNFSF15 activity in the gut and whether it improves IBD through them deserve further research [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702851/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The potential benefits of butyrate can be obtained by ingesting dietary fibers (especially resistant starches), taking probiotics that restore the gut microbiota or supplementing with sodium butyrate.</span></p> <h4><strong>Omega-3 Fatty Acids</strong></h4> <p><span style="font-weight: 400;">High intake of </span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">omega-3s</span></a><span style="font-weight: 400;"> from fish (EPA and </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;">) may be protective against the development of IBD, especially ulcerative colitis. In the case of Crohn&rsquo;s disease, they seem to help prevent it and keep it in remission, but it&rsquo;s unclear whether they can improve the symptoms once the condition has developed and progressed [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29543869"><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><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> <p><span style="font-weight: 400;">However, meta-analyses concluded that further, higher-quality research is needed before omega-3s can be recommended as a complementary strategy to manage IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20564531/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22591898/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">These fatty acids reduced the production of inflammatory cytokines, including IL-23, in mice and cells. In chicken, dietary supplementation with </span><a href="http://selfhacked.com/blog/glycine-little-protein/"><span style="font-weight: 400;">glycine</span></a><span style="font-weight: 400;"> and fish reduced the levels of TNFSF15 and other inflammatory markers [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055457/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854360/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19735017"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Moreover, they inhibited the Th1 and Th17 immune responses in mice [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578775/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854360/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650034/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Foods rich in omega-3 fatty acids especially include fatty fish such as salmon, mackerel, sardines, herrings, and tuna.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Avoiding FODMAPs and eating resistant starch and fish rich in omega-3 fatty acids may help control IBD and reduce TNFSF15 activity.</span></p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Managing Stress</strong></h4> <p><span style="font-weight: 400;">Psychological </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;"> has well-known detrimental effects on gut health and inflammation. It raises gut permeability and the levels of different inflammatory cytokines, including some associated with TNFSF15 such as </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="http://selfhacked.com/blog/th17/"><span style="font-weight: 400;">IL-17</span></a><span style="font-weight: 400;">, and </span><a href="https://www.selfhacked.com/blog/interferon-gamma-how-to-increase-decrease-high-low-levels/"><span style="font-weight: 400;">IFN-&gamma;</span></a><span style="font-weight: 400;">. Additionally, chronic stress enhances the Th17 immune response [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777426/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262626/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20709414"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28886500"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30980732"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/abs/pii/S0889159113000524"><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 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 [</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> <h4><strong>Drinking Less Alcohol</strong></h4> <p><span style="font-weight: 400;">Several studies have associated high alcohol consumption with symptom worsening and flare-ups in people with IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708696/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774231/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191867/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29195675"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Chronic alcohol consumption activated the Th1 immune response in animal studies [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299637/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16573591"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">What&rsquo;s more, a post-mortem study of the brains of alcoholics found increased levels of the TNFSF15 receptor DR3 in the hippocampus [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/32139808"><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;">Properly managing stress and avoiding alcohol abuse helps with gut inflammation and may reduce TNFSF15 activity.</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>Probiotics</strong></h4> <p><span style="font-weight: 400;">People with IBD often have impaired </span><a href="https://www.selfhacked.com/blog/gut-bacteria-microbiome/"><span style="font-weight: 400;">gut microbiome</span></a><span style="font-weight: 400;">, which may worsen their disease. In a meta-analysis, a blended</span> <a href="https://selfhacked.com/blog/probiotics-good-bacteria/"><span style="font-weight: 400;">probiotic</span></a><span style="font-weight: 400;"> containing</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><a href="https://selfhacked.com/blog/b-longum/"><em><span style="font-weight: 400;">Bifidobacterium</span></em></a><span style="font-weight: 400;"> strains increased remission rates by 1.7x in ulcerative colitis patients [</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 Asian studies involving patients with ulcerative colitis, a </span><a href="https://selfhacked.com/blog/b-subtilis/"><em><span style="font-weight: 400;">Bacillus subtilis</span></em></a> <span style="font-weight: 400;">probiotic significantly reduced the number of days with bloody stool, led to complete remission without relapse, and significantly increased the efficacy of mesalazine or sulfasalazine therapy [</span><a href="https://www.wageningenacademic.com/doi/pdf/10.3920/BM2008.1005"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In chicken challenged with bacterial lipopolysaccharide (</span><a href="https://www.selfhacked.com/blog/lipopolysaccharides/"><span style="font-weight: 400;">LPS</span></a><span style="font-weight: 400;">), a probiotic with </span><a href="http://selfhacked.com/blog/b-subtilis/"><em><span style="font-weight: 400;">B. subtilis</span></em></a><span style="font-weight: 400;"> attenuated the increase in TNFSF15 levels and preserved gut barrier function [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28505587"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Several studies in animals and cells found that probiotics can reduce the inflammatory response caused by Th1 and Th17 cells [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21257218"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351195/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613231/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Andrographis</strong></h4> <p><a href="http://selfhacked.com/blog/top-12-scientific-benefits-of-andrographis-paniculata-including-dosage-safety-and-side-effects/"><em><span style="font-weight: 400;">Andrographis paniculata</span></em></a><span style="font-weight: 400;">, known as the &ldquo;King of</span><a href="https://selfhacked.com/blog/herbal-bitters/"> <span style="font-weight: 400;">Bitters</span></a><span style="font-weight: 400;">&rdquo;, is traditionally used in Ayurveda and Chinese medicine. It may improve the symptoms of ulcerative colitis [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23292349"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In two clinical trials, </span><a href="http://selfhacked.com/blog/top-12-scientific-benefits-of-andrographis-paniculata-including-dosage-safety-and-side-effects/"><span style="font-weight: 400;">andrographolide</span></a><span style="font-weight: 400;">, the active ingredient in andrographis, improved ulcerative colitis by suppressing the IL-23/</span><a href="http://selfhacked.com/blog/th17/"><span style="font-weight: 400;">IL-17</span></a><span style="font-weight: 400;"> axis [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835811/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29749556"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Andrographis extract prevented colitis in mice by inhibiting the Th1 and Th17 responses. Its active compound andrographolide had a similar inhibitory effect on these responses in blood cells from patients with ulcerative colitis [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465822/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29749556"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Taking 1,200 - 1,800 mg andrographis daily for 8 weeks reduced the symptoms of mild-to-moderate colitis in adults, with the 1,800 mg dose being more effective. However, it did not affect remission rates any more than placebo [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538174/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Astragalus</strong></h4> <p><span style="font-weight: 400;">Both oral and colonic </span><a href="https://selfhacked.com/blog/astragalus/"><span style="font-weight: 400;">astragalus </span></a><span style="font-weight: 400;">(</span><em><span style="font-weight: 400;">A. membranaceus</span></em><span style="font-weight: 400;">) treatments protected against colitis (colon inflammation) in rats by reducing tissue damage and the production of inflammatory cytokines [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19539495"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789992/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Its active component astragaloside reduced </span><em><span style="font-weight: 400;">TNFSF15 </span></em><span style="font-weight: 400;">expression in mice with heart inflammation caused by a viral infection [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25769323"><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 on almost 150 asthmatic children, astragalus (as an add-on to conventional therapy) improved the symptoms by reducing the number of Th17 cells while increasing Tregs [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/31076129"><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;">Preliminary research suggests that probiotics, andrographis, and astragalus may help with IBD in part by reducing TNFSF15 activity.</span></p>
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182 | content_learn_more_2984402296885080_text == Based on the variants we looked at, your TNFSF15 gene is associated with somewhat higher IBD rates. However, this doesn't necessarily reflect your overall risk of IBD, just one gene related to it. Avoiding stress, excess alcohol, and FODMAP-rich foods while taking omega-3 fatty acids and supplements may reduce gut inflammation. Keep reading to learn more.
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