Sangfuang, Nannapat;
McCoubrey, Laura E;
Awad, Atheer;
Marzorati, Massimo;
Ghyselinck, Jonas;
Verstrepen, Lynn;
De Munck, Julie;
... Basit, Abdul W; + view all
(2025)
Effects of senotherapeutics on gut microbiome dysbiosis and intestinal inflammation in Crohn's disease: A pilot study.
Translational Research
, 278
pp. 36-47.
10.1016/j.trsl.2025.02.004.
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Abstract
Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, and is usually accompanied by dysbiosis in the gut microbiome, a factor that contributes to disease progression. Excessive production of reactive oxygen species (ROS) because of gut microbiome dysbiosis-one of the hallmark features of IBD-promotes chronic inflammation and facilitates the transformation of normal cells into senescent cells. Cellular senescence is associated with the development of various chronic and age-related diseases. We hypothesise that senolytic agents, specifically dasatinib (D) and quercetin (Q), could have a beneficial effect on both the gut microbiome and intestinal cells in IBD. The modulatory effects of a combination of D+Q was assessed in the M-SHIME model with faecal microbiota sourced from Crohn's disease patients. D+Q significantly modulated butyrate and lactate levels in the samples from specific patients. In addition, metabolomic analysis showed that D+Q positively impacted the abundance of anti-inflammatory bacteria while also significantly reducing the several species of pathogenic bacteria. Findings from a Caco-2 cell/THP1 co-culture model of IBD demonstrated that D+Q exerted strong immunomodulatory effects on the gut epithelium, evidenced by reduced NF-kB activity, and lower levels of the pro-inflammatory markers TNF-α, CXCL-10, and MCP-1. Furthermore, D+Q induced the secretion of anti-inflammatory cytokines, including IL-6 and IL-10. However, it should be noted that D+Q also led to the secretion of the pro-inflammatory cytokines IL-8. These findings suggest that D+Q could offer a novel therapeutic approach for advanced IBD management by modulating both the gut microbiome and inflammatory pathways. The results support the potential repurposing of senotherapeutic agents as a strategy for addressing the chronic inflammation central to IBD pathogenesis.
| Type: | Article |
|---|---|
| Title: | Effects of senotherapeutics on gut microbiome dysbiosis and intestinal inflammation in Crohn's disease: A pilot study |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.trsl.2025.02.004 |
| Publisher version: | https://doi.org/10.1016/j.trsl.2025.02.004 |
| Language: | English |
| Additional information: | Copyright © 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Inflammatory Bowel Disease, Senolytic cocktail, Senotherapeutics, ageing, gut health, human gut microbiome, aged colon |
| 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/10205441 |
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