{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:52:16Z","timestamp":1772632336526,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018353","name":"European Crohn's and Colitis Organisation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018353","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD) is commonly treated with biologic therapies, including anti-TNF\u03b1 agents, vedolizumab (VDZ), and ustekinumab (USTE), yet only a subset of patients respond to these treatments. This study aimed to evaluate the potential of the gut microbiome to predict treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adult CD patients initiating anti-TNF\u03b1 (infliximab or adalimumab), VDZ or USTE were enrolled. Pre-treatment ileal and\/or colonic biopsies were collected endoscopically. Treatment response after 26\u201352 weeks was defined by \u226550% reduction in the simple endoscopic score for CD and either a corticosteroid-free clinical response (\u22653-point HBI decrease or remission [HBI \u22644] without systemic steroids) or a biochemical response (\u226550% or \u22645 mg\/L CRP reduction and \u226550% or \u2264250 \u03bcg\/g faecal calprotectin reduction) versus baseline. Mucosal microbiota was profiled by 16S rRNA gene sequencing of biopsies. Machine learning models predicting treatment response were trained using ASV-level count data. The impact of heat-killed bacteria on anti-TNF\u03b1\u2013induced CD14\n                      <jats:sup>+<\/jats:sup>\n                      CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophages was tested in mixed lymphocyte reactions (MLRs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 125 patients were included: 39 on anti-TNF\u03b1, 47 on VDZ, and 39 on USTE. Clinical features were similar between responders and non-responders, aside from sex (USTE-colon) and CRP (USTE-ileum). No major microbial differences were observed in VDZ, USTE ileal or colon samples. However, in colonic biopsies, anti-TNF\u03b1 responders had significantly higher pre-treatment \u03b1-diversity, and 3.9% of \u03b2-diversity variation associated with response. Among six models, the anti-TNF\u03b1 colonic model performed significantly better than random (AUC = 0.90) to predict response.\n                      <jats:italic>Mediterraneibacter gnavus<\/jats:italic>\n                      ASVs associated with non-response, whereas\n                      <jats:italic>Blautia<\/jats:italic>\n                      ASVs associated with response, to anti-TNF\u03b1. When tested in MLRs, pretreatment with\n                      <jats:italic>M. gnavus<\/jats:italic>\n                      and\n                      <jats:italic>B. luti<\/jats:italic>\n                      led to a reduction in macrophage polarization, with a significantly stronger effect observed for\n                      <jats:italic>M. gnavus<\/jats:italic>\n                      compared with\n                      <jats:italic>B. luti<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Taken together, this study demonstrates that the colonic mucosal microbiome prior to anti-TNF\u03b1 treatment can distinguish responders from non-responders in CD, supporting its potential as a predictive biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1741002","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:00:05Z","timestamp":1772607605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Colonic biopsy-associated microbial signatures are predictive of response to anti-TNF\u03b1 biological therapy in Crohn\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Konstantina","family":"Zafeiropoulou","sequence":"first","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]},{"name":"Department of Pediatric Surgery, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ishtu L.","family":"Hageman","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]},{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianqi","family":"Mu","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Davids","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Y. F.","family":"Li Yim","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]},{"name":"Department of Pediatric Surgery, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent W.","family":"Joustra","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodorus B. M.","family":"Hakvoort","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Satsangi","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Chronas","sequence":"additional","affiliation":[{"name":"Independent Researcher","place":["Delft, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pim J.","family":"Koelink","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon E.","family":"Wildenberg","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene M.","family":"van den Wijngaard","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert R.","family":"D\u2019Haens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter J.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]},{"name":"Department of General, Visceral-, Thoracic and Vascular Surgery, University Hospital Bonn","place":["Bonn, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1053\/j.gastro.2019.07.025","article-title":"Metabolic functions of gut microbes associate with efficacy of tumor necrosis factor antagonists in patients with inflammatory bowel diseases","volume":"157","author":"Aden","year":"2019","journal-title":"Gastroenterology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/s0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. 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