{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:04Z","timestamp":1787029204953,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangdong Province, China","award":["2019A1515012115"],"award-info":[{"award-number":["2019A1515012115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Inflammatory Bowel Disease (IBD) is a severe relapsing inflammation of the gastrointestinal tract. The association between fatty acids (FAs) and IBD is controversial and it remains unclear whether there is a causal relationship between them. Mendelian randomization (MR) analysis was province\/state for affiliations from the same country performed to clarify the causality. Eligible single nucleotide polymorphisms were selected as instrumental variables from six Genome-wide association studies, involving 114,999 individuals in UK Biobank. The summary-level data on IBD, including Crohn\u2019s disease (CD) and ulcerative colitis (UC), were obtained from the International Inflammatory Bowel Disease Genetics Consortium with 20,883 and 27,432 individuals involved. The primary inverse variance weighted (IVW) method as well as other supplementary analysis ones were adopted to evaluate the causal relationship between diverse FAs and IBD. The tests for heterogeneity and pleiotropy, and Leave-one-out analysis were adopted to verify the stability of the results. Omega-3 FA was found to have a causal effect on UC instead of CD. For each Standard Deviation increase in Omega-3 FA genetic levels, the risk of ulcerative colitis was found to be reduced by 39.9% by the IVW method (p = 1.766 \u00d7 10\u22124), by 57.8% by the MR Egger (p = 1.11 \u00d7 10\u22122), by 51.5% by the Weighted median estimator (p = 7.706 \u00d7 10\u22124), by 39% by the Maximum likelihood estimation (p = 3.262 \u00d7 10\u22124), and by 54.5% by the penalized weighted median estimator (p = 1.628 \u00d7 10\u22124). No causal relationship was found between other FAs (including total FA, saturated FA, polyunsaturated FA, monounsaturated FA and omega-6 FA) and IBD. The pleiotropic test and Leave-one-out analysis both proved the validity and reliability of these MR analyses. Omega-3 FA was observed to have a protective effect against UC, providing a new perspective on the investigation of the associations between FAs and IBD.<\/jats:p>","DOI":"10.3390\/nu14142883","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T01:57:11Z","timestamp":1657850231000},"page":"2883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Effects of Fatty Acids on Inflammatory Bowel Disease: A Two-Sample Mendelian Randomization Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-2605","authenticated-orcid":false,"given":"Jian","family":"He","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwei","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/S0140-6736(16)32126-2","article-title":"Ulcerative colitis","volume":"389","author":"Ungaro","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.disamonth.2017.07.001","article-title":"A comprehensive review and update on Crohn\u2019s disease","volume":"64","author":"Gajendran","year":"2018","journal-title":"Disease-A-Month"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1901269","DOI":"10.1002\/mnfr.201901269","article-title":"Nutritional Lipids and Mucosal Inflammation","volume":"65","author":"Wawrzyniak","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1053\/j.gastro.2013.12.034","article-title":"Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn\u2019s disease","volume":"146","author":"Costea","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/ajg.2011.44","article-title":"Dietary intake and risk of developing inflammatory bowel disease: A systematic review of the literature","volume":"106","author":"Hou","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1053\/j.gastro.2016.10.019","article-title":"Diet as a Trigger or Therapy for Inflammatory Bowel Diseases","volume":"152","author":"Lewis","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1038\/s41598-019-39232-z","article-title":"Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn\u2019s Disease","volume":"9","author":"Scoville","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1136\/gutjnl-2013-305304","article-title":"Long-term intake of dietary fat and risk of ulcerative colitis and Crohn\u2019s disease","volume":"63","author":"Ananthakrishnan","year":"2014","journal-title":"Gut"},{"key":"ref_10","unstructured":"Burgess, S., and Thompson, S.G. (2021). Mendelian Randomization: Methods for Causal Inference Using Genetic Variants, CRC Press."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119.e115","DOI":"10.1016\/j.neurobiolaging.2020.10.022","article-title":"Causal relationships between gut metabolites and Alzheimer\u2019s disease: A bidirectional Mendelian randomization study","volume":"100","author":"Zhuang","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sazonovs, A., Stevens, C.R., Venkataraman, G.R., Yuan, K., Avila, B., Abreu, M.T., Ahmad, T., Allez, M., Atzmon, G., and Baras, A. (2021). Sequencing of over 100,000 individuals identifies multiple genes and rare variants associated with Crohns disease susceptibility. medRxiv.","DOI":"10.1101\/2021.06.15.21258641"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_16","unstructured":"Wooldridge, J. (2009). Instrumental variables estimation and two stage least squares. Introductory Econometrics: A Modern Approach, South-Western."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/genetics\/163.3.1153","article-title":"Maximum-likelihood estimation of relatedness","volume":"163","author":"Milligan","year":"2003","journal-title":"Genetics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hemani, G., Bowden, J., Haycock, P., Zheng, J., Davis, O., Flach, P., Gaunt, T., and Smith, G.D. (2017). Automating Mendelian randomization through machine learning to construct a putative causal map of the human phenome. bioRxiv, 173682.","DOI":"10.1101\/173682"},{"key":"ref_21","unstructured":"Burgess, S., Bowden, J., Dudbridge, F., and Thompson, S.G. (2016). Robust instrumental variable methods using multiple candidate instruments with application to Mendelian randomization. arXiv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/00054725-200502000-00009","article-title":"Dietary risk factors for inflammatory bowel disease: A multicenter case-control study in Japan","volume":"11","author":"Sakamoto","year":"2005","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"111448","DOI":"10.1016\/j.mce.2021.111448","article-title":"The role of fatty acids in Crohn\u2019s disease pathophysiology\u2014An overview","volume":"538","author":"Piotrowska","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e066452","DOI":"10.1136\/bmj-2021-066452","article-title":"Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial","volume":"376","author":"Hahn","year":"2022","journal-title":"BMJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/s41467-019-08711-2","article-title":"The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes","volume":"10","author":"Luu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3389\/fimmu.2019.00115","article-title":"Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis","volume":"10","author":"Cluxton","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40169-017-0153-6","article-title":"Significance of long chain polyunsaturated fatty acids in human health","volume":"6","author":"Tejera","year":"2017","journal-title":"Clin. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.bbalip.2014.08.010","article-title":"Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance","volume":"1851","author":"Calder","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"964","DOI":"10.3945\/jn.110.132985","article-title":"Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation of EPA into white blood cells and modulates immune responses within one week in healthy men and women","volume":"141","author":"Faber","year":"2011","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"748","DOI":"10.3945\/ajcn.112.041343","article-title":"Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish","volume":"96","author":"Browning","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1476-511X-9-12","article-title":"Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family","volume":"9","author":"Kong","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27384","DOI":"10.1074\/jbc.M109.044065","article-title":"Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner","volume":"284","author":"Wong","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.imbio.2008.07.015","article-title":"The many faces of PPARgamma: Anti-inflammatory by any means?","volume":"213","author":"Szanto","year":"2008","journal-title":"Immunobiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.1","article-title":"Guidelines for performing Mendelian randomization investigations","volume":"4","author":"Burgess","year":"2019","journal-title":"Wellcome Open Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/14\/2883\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:50:05Z","timestamp":1760140205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/14\/2883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":34,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["nu14142883"],"URL":"https:\/\/doi.org\/10.3390\/nu14142883","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]}}}