{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:58:55Z","timestamp":1787921935619,"version":"build-2784847793"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health (RB and MP)","award":["ROL 32612 (RB)"],"award-info":[{"award-number":["ROL 32612 (RB)"]}]},{"name":"Compagnia di San Paolo","award":["ROL 32612 (RB)"],"award-info":[{"award-number":["ROL 32612 (RB)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon, often associated with gut microbial dysbiosis. Although anti-TNF-\u03b1 agents, such as Adalimumab (Cinnora\u00ae), are used to treat moderate-to-severe UC, the treatment response is highly variable. Identifying early microbial biomarkers of response could help support personalized therapeutic strategies and prevent unnecessary exposure to ineffective treatments. However, the long-term effects of anti-TNF therapy on both stool and mucosal microbiota remain poorly understood. This prospective longitudinal study included 23 corticosteroid-refractory or -dependent UC patients who started Adalimumab after endoscopy-confirmed flare-ups. Stool samples and inflamed colonic biopsies were collected at baseline, and 3 and 6 months. Microbiota profiling was performed using 16S rRNA sequencing. Microbial changes were analyzed over time and compared between responders (Mayo score 0\u20131) and non-responders (Mayo score \u2265 2). Sixty percent of patients achieved clinical remission. In responders, stool microbiota showed increased Bacteroidetes and decreased Proteobacteria abundances, along with an enrichment of beneficial taxa including Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila. Mucosal microbiota exhibited persistent dysbiosis, characterized by an increase in Proteobacteria and a reduced Firmicutes\/Proteobacteria ratio. Notably, responders showed distinct compartment-specific microbial changes, with a decrease in Gammaproteobacteria in stool and an increase in Corynebacterium in tissue. Adalimumab induces divergent microbial changes in stool and mucosa. While stool microbiota trends toward eubiosis in responders, persistent mucosal dysbiosis may reflect asymptomatic inflammation. These findings underscore the importance of niche-specific microbiome profiling in UC and support its integration into personalized treatment monitoring.<\/jats:p>","DOI":"10.3390\/microorganisms13081941","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"1941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Predictive Microbial Markers Distinguish Responders and Non-Responders to Adalimumab: A Step Toward Precision Medicine in Ulcerative Colitis"],"prefix":"10.3390","volume":"13","author":[{"given":"Shaghayegh Baradaran","family":"Ghavami","sequence":"first","affiliation":[{"name":"IBD Department, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-0190","authenticated-orcid":false,"given":"Arfa","family":"Moshiri","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Bonaretti","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-733X","authenticated-orcid":false,"given":"Maryam","family":"Farmani","sequence":"additional","affiliation":[{"name":"IBD Department, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-3383","authenticated-orcid":false,"given":"Margherita","family":"Squillario","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16131 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddi","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Central Laboratory, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Shahrokh","sequence":"additional","affiliation":[{"name":"IBD Department, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedieh","family":"Balaii","sequence":"additional","affiliation":[{"name":"IBD Department, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7316-0772","authenticated-orcid":false,"given":"Maria Valeria","family":"Corrias","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-4286","authenticated-orcid":false,"given":"Mirco","family":"Ponzoni","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"IBD Department, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-8166","authenticated-orcid":false,"given":"Roberto","family":"Biassoni","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Park, Y.E., Moon, H.S., Yong, D., Seo, H., Yang, J., Shin, T.S., Kim, Y.K., Kim, J.R., Lee, Y.N., and Kim, Y.H. (2022). Microbial changes in stool, saliva, serum, and urine before and after anti-TNF-\u03b1 therapy in patients with inflammatory bowel diseases. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-10450-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1097\/00054725-200810001-00005","article-title":"Inflammatory bowel disease: The difference between children and adults","volume":"14","author":"Kelsen","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: Current state of the art","volume":"13","author":"Fiocchi","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Olfatifar, M., Zali, M.R., Pourhoseingholi, M.A., Balaii, H., Ghavami, S.B., Ivanchuk, M., Ivanchuk, P., Nazari, S.H., Shahrokh, S., and Sabour, S. (2021). The emerging epidemic of inflammatory bowel disease in Asia and Iran by 2035: A modeling study. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-01745-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.20805.1","article-title":"Ulcerative colitis: Recent advances in the understanding of disease pathogenesis","volume":"9","author":"Porter","year":"2020","journal-title":"F1000Research"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pagnini, C., Pizarro, T.T., and Cominelli, F. (2019). Novel Pharmacological Therapy in Inflammatory Bowel Diseases: Beyond Anti-Tumor Necrosis Factor. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00671"},{"key":"ref_8","first-page":"1433","article-title":"Natalizumab in the treatment of Crohn\u2019s disease patients","volume":"17","author":"Pagnini","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/MIB.0000000000000202","article-title":"Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: Evolution in the definition and management of primary nonresponse","volume":"21","author":"Papamichael","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1152\/physrev.00045.2009","article-title":"Gut microbiota in health and disease","volume":"90","author":"Sekirov","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41575-019-0248-1","article-title":"Host-microbiota interactions in inflammatory bowel disease","volume":"17","author":"Neurath","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature11319","article-title":"Gut microbiota composition correlates with diet and health in the elderly","volume":"488","author":"Claesson","year":"2012","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41591-018-0308-z","article-title":"Microbial network disturbances in relapsing refractory Crohn\u2019s disease","volume":"25","author":"Yilmaz","year":"2019","journal-title":"Nat. Med."},{"key":"ref_14","first-page":"673","article-title":"Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis","volume":"104","author":"Ho","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1056\/NEJMoa050516","article-title":"Infliximab for induction and maintenance therapy for ulcerative colitis","volume":"353","author":"Rutgeerts","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtbi.2016.03.016","article-title":"Improving the microbial community reconstruction at the genus level by multiple 16S rRNA regions","volume":"398","author":"Wang","year":"2016","journal-title":"J. Theor. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W180","DOI":"10.1093\/nar\/gkx295","article-title":"MicrobiomeAnalyst\u2014A web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data","volume":"45","author":"Dhariwal","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41596-019-0264-1","article-title":"Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data","volume":"15","author":"Chong","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/nar\/gkad407","article-title":"MicrobiomeAnalyst 2.0: Comprehensive statistical, functional, and integrative analysis of microbiome data","volume":"51","author":"Lu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cao, K.-A.L., Costello, M.-E., Lakis, V.A., Bartolo, F., Chua, X.-Y., Brazeilles, R., and Rondeau, P. (2016). MixMC: A Multivariate Statistical Framework to Gain Insight into Microbial Communities. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160169"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00219-18","DOI":"10.1128\/msystems.00219-18","article-title":"q2-longitudinal: Longitudinal and Paired-Sample Analyses of Microbiome Data","volume":"3","author":"Bokulich","year":"2018","journal-title":"mSystems"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","article-title":"KEGG as a reference resource for gene and protein annotation","volume":"44","author":"Kanehisa","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D633","DOI":"10.1093\/nar\/gkx935","article-title":"The MetaCyc Database of metabolic pathways and enzymes","volume":"46","author":"Caspi","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.2337\/dc18-0777","article-title":"Intestinal metaproteomics reveals host-microbiota interactions in subjects at risk for type 1 diabetes","volume":"41","author":"Gavin","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"dgaa407","DOI":"10.1210\/clinem\/dgaa407","article-title":"Gut Microbiota in T1DM-Onset Pediatric Patients: Machine-Learning Algorithms to Classify Microorganisms as Disease Linked","volume":"105","author":"Biassoni","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1128\/IAI.00331-12","article-title":"FimA, FimF, and FimH are necessary for assembly of type 1 fimbriae on Salmonella enterica serovar Typhimurium","volume":"80","author":"Zeiner","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev.micro.60.080805.142106","article-title":"Curli biogenesis and function","volume":"60","author":"Barnhart","year":"2006","journal-title":"Ann. Rev. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dahal, R.H., Kim, S., Kim, Y.K., Kim, E.S., and Kim, J. (2023). Insight into gut dysbiosis of patients with inflammatory bowel disease and ischemic colitis. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1174832"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1093\/ecco-jcc\/jjv223","article-title":"Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis","volume":"10","author":"Alipour","year":"2016","journal-title":"J. Crohns Colitis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"104158","DOI":"10.1016\/j.isci.2022.104158","article-title":"Bacteroides ovatus colonization influences the abundance of intestinal short chain fatty acids and neurotransmitters","volume":"25","author":"Horvath","year":"2022","journal-title":"iScience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.ajpath.2021.01.009","article-title":"Bacteroides ovatus Promotes IL-22 Production and Reduces Trinitrobenzene Sulfonic Acid-Driven Colonic Inflammation","volume":"191","author":"Ihekweazu","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hiippala, K., Barreto, G., Burrello, C., Diaz-Basabe, A., Suutarinen, M., Kainulainen, V., Bowers, J.R., Lemmer, D., Engelthaler, D.M., and Eklund, K.K. (2020). Novel odoribacter splanchnicus strain and its outer membrane vesicles exert immunoregulatory effects in vitro. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.575455"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2217\/fmb-2016-0130","article-title":"Roseburia spp.: A marker of health?","volume":"12","author":"Smida","year":"2017","journal-title":"Future Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","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 antagonist in patients with Inflammatory Bowel Diseases","volume":"157","author":"Aden","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1128\/br.27.1.56-71.1963","article-title":"Healthy carriage of Staphylococcus aureus: Its prevalence and importance","volume":"27","author":"Williams","year":"1963","journal-title":"Bacteriol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/mi.2016.75","article-title":"Mechanisms of inflammation-driven bacterial dysbiosis in the gut","volume":"10","author":"Zeng","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lee, S.A., Liu, F., Yuwono, C., Phan, M., Chong, S., Biazik, J., Tay, A.C.Y., Janitz, M., Riordan, S.M., and Lan, R. (2023). Emerging Aeromonas enteric infections: Their association with inflammatory bowel disease and novel pathogenic mechanisms. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.01088-23"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Baldelli, V., Scaldaferri, F., Putignani, L., and Del Chierico, F. (2021). The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases. Microorganisms, 9.","DOI":"10.3390\/microorganisms9040697"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/ecosalplus.8.3.2.6","article-title":"Type 1 Fimbriae, Curli, and Antigen 43: Adhesion, Colonization, and Biofilm Formation","volume":"1","author":"Klemm","year":"2004","journal-title":"EcoSal Plus"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/8\/1941\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:31:45Z","timestamp":1760034705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/8\/1941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["microorganisms13081941"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13081941","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}