Favaron, Alessia;
Sangfuang, Nannapat;
McCoubrey, Laura E;
Awad, Atheer;
Ghyselinck, Jonas;
Marzorati, Massimo;
Verstrepen, Lynn;
... Orlu, Mine; + view all
(2026)
Assessing the effects of tofacitinib on the gut microbiome in inflammatory bowel disease.
European Journal of Pharmaceutical Sciences
, 216
, Article 107365. 10.1016/j.ejps.2025.107365.
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Abstract
Gut microbiota dysbiosis and impaired epithelial barrier function play a key role in inflammatory bowel disease (IBD). Tofacitinib citrate, a Janus kinase (JAK) inhibitor approved for IBD, modulates immune responses via the JAK-STAT (Janus kinase–signal transducer and activator of transcription) pathway, yet its effects on the gut microbiome remain unclear. Here, we employed the short-term colon model (ProDigest, BE) containing human microbiota from three Crohn’s Disease donors to assess fermentative and metabolic activities and microbial composition following 48 h of tofacitinib treatment. A Caco-2/THP1 co-culture system was used to assess the impact of tofacitinib on epithelial immunomodulation and barrier integrity. Tofacitinib did not significantly affect microbiota composition and fermentative or metabolic activity. However, it consistently reduced pro-inflammatory chemokines motif chemokine ligand 10 (CXCL10) and monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in specific donors, indicating targeted immunomodulatory effects. These findings suggest that while tofacitinib may have a minimal impact on microbiota function, it may exert anti-inflammatory effects via microbiota-derived metabolites. The short-term colon model represents a robust platform for investigating microbiome-drug interactions relevant to IBD.
| Type: | Article |
|---|---|
| Title: | Assessing the effects of tofacitinib on the gut microbiome in inflammatory bowel disease |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejps.2025.107365 |
| Publisher version: | https://doi.org/10.1016/j.ejps.2025.107365 |
| Language: | English |
| Additional information: | © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Crohn’s Disease, Gut microbiome, Inflammatory Bowel Disease, JAK Inhibitor, SHIME, Short-term colon, Tofacitinib citrate |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217181 |
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