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Alterations in the gut microbiome are a consistent feature of UC, yet their causal contribution to disease onset and progression remains unresolved. Current animal models rely largely on chemical or genetic induction and fail to capture the complexity of host-microbiome interactions characteristic of human disease. To address this limitation and enhance the translational relevance of preclinical research, this study employed patient-derived microbiota to model UC-associated dysbiosis and investigated its effects alone and in combination with chemical induction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We compared three mouse models using different UC-induction triggers: dextran sulphate sodium (DSS), faecal microbiota transplantation (FMT) from a UC patient, and their combination (COMB). DSS and COMB treatments induced marked clinical symptoms, whereas FMT alone caused only mild changes, likely due to the short exposure period. Immunophenotyping revealed distinct immune profiles across all models, with leukocyte and neutrophil infiltration in the colonic mucosa of all groups, demonstrating that the microbiota alone can elicit localized immune activation. Transcriptomic analysis showed that FMT significantly modulated tight junction and mucin gene expression and induced microbiome shifts resembling those observed in human UC. In contrast, DSS triggered a strong pro-inflammatory transcriptional response and reduced microbial diversity, but with compositional changes mostly opposing those seen in UC patients. The COMB model combined features of both approaches \u2013 producing clinical symptoms and inflammatory activation similar to DSS and tight junction dysregulation resembling FMT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study investigated novel experimental models of ulcerative colitis by incorporating patient-derived microbiota as an inducing factor. DSS induced strong clinical and inflammatory responses, FMT primarily altered barrier gene expression and microbiome composition, and their combination merged both inflammatory and epithelial characteristics. These microbiota-based models show promise for more accurately reproducing UC pathophysiology and thereby improving translational relevance. Further optimization is needed, including adjustment of exposure duration and sequence of induction, as well as validation for reproducibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42826-026-00283-9","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:55:12Z","timestamp":1780912512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring new animal models of ulcerative colitis: evaluating chemical and patient-derived microbial triggers to advance translational relevance"],"prefix":"10.1186","volume":"42","author":[{"given":"Maria","family":"Rynikova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Gancarcikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Lauko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Mudronova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Adamkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Janicko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8244-6740","authenticated-orcid":false,"given":"Vlasta","family":"Demeckova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"3","key":"283_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1111\/jgh.14872","volume":"35","author":"WY Mak","year":"2020","unstructured":"Mak WY, Zhao M, Ng SC, Burisch J. 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All animals were treated and euthanized humanely, adhering to the ethical guidelines set forth by the Ethics Committee of the University of Veterinary Medicine and Pharmacy in Kosice). All experimental procedures and reporting in this study comply with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. All animals were euthanized humanely by cervical dislocation performed by trained personnel in accordance with the AVMA Guidelines for the Euthanasia of Animals: 2020 Edition [\n                      \n                      ]. UC FMT donor screening, selection and sample collection was approved by the Ethical Commission of the University Hospital of L. Pasteur in Kosice, Slovakia (project No. 14\/2018\/OVaV).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from the FMT donor for the collection and use of faecal samples in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21"}}