{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T08:05:30Z","timestamp":1779264330178,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":139,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474457"],"award-info":[{"award-number":["82474457"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Although gut microbiota dysbiosis has been associated with irritable bowel syndrome (IBS), the specific roles of individual bacterial strains in the pathogenesis of IBS remain incompletely elucidated. Additionally, whether these bacterial strains exert their effects through the ferroptosis pathway remains unclear. Therefore, this study is aimed at investigating the impact of ferroptosis\u2010related molecules regulated by gut microbiota on IBS development using Mendelian randomization (MR) mediation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genome\u2010wide association study (GWAS) data for gut microbiota were acquired from the FINRISK study, and protein quantitative trait loci (pQTL) data were retrieved from the deCODE database. Ferroptosis\u2010related genes and their downstream molecules were identified using the FerrDb V2 database; these molecules were then intersected with pQTL data to obtain ferroptosis\u2010related pQTLs. IBS datasets were derived from the FinnGen R12 database. A two\u2010step MR mediation analysis was performed, with the inverse\u2010variance weighted (IVW) method designated as the primary analytical approach. Eligible results were defined by three criteria:\n                      <jats:italic>p<\/jats:italic>\n                      value &lt;\u20090.05, mediation proportion &gt;\u200910%, and consistency between mediation effects and total effects. Heterogeneity analysis, pleiotropy testing, and sensitivity analysis were further conducted to verify the robustness of the results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Bifidobacterium breve<\/jats:italic>\n                      exhibited a negative correlation with v\u2010erb\u2010b2 avian erythroblastic leukemia viral oncogene Homolog 1 (ERBB1) (beta1 = \u22120.125). In turn, ERBB1 was negatively correlated with IBS (beta2 = \u22120.223), whereas\n                      <jats:italic>Bifidobacterium breve<\/jats:italic>\n                      showed a positive total effect on IBS (beta_all = 0.168). The mediation proportion of this pathway was 16.57% (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Bifidobacterium breve<\/jats:italic>\n                      may promote the pathogenesis of IBS by downregulating ERBB1, suggesting that increased ferroptosis susceptibility in intestinal epithelial cells may play a role in this pathway. This finding provides novel insights into the underlying mechanisms of IBS and may offer a potential target for IBS intervention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/6705631","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T07:07:52Z","timestamp":1779260872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Bifidobacterium breve<\/i>\n                    Promotes the Pathogenesis of IBS by Downregulating the Expression of Ferroptosis\u2010Related Molecule ERBB1: A Mendelian Randomization Mediation Analysis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1484-9983","authenticated-orcid":false,"given":"Lian","family":"Mo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8325-9346","authenticated-orcid":false,"given":"Yue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-6951","authenticated-orcid":false,"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8079-5569","authenticated-orcid":false,"given":"Youcheng","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1437-9969","authenticated-orcid":false,"given":"Lifeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4032-6039","authenticated-orcid":false,"given":"Chunyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6454-6053","authenticated-orcid":false,"given":"Shuyu","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3728-2083","authenticated-orcid":false,"given":"Jianye","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v29.i26.4120"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000523"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.658354"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.10.035"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2299-1"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1902719"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/add.14038"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00757-1"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00991-z"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00978-w"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22522"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.040"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.729346"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c04602"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21746-8"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14183671"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16209"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252312487"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2021.1876631"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S492290"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.06.242"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.06.011"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2022.2104085"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2021-0883"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2024.14431"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05007-0"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-020-0182-y"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.10.270"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202204006"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.09.012"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2263210"},{"key":"e_1_2_14_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06592-6"},{"key":"e_1_2_14_37_2","doi-ass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