ArticleScientific reports2021
Development of a self-limiting model of methotrexate-induced mucositis reinforces butyrate as a potential therapy.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Image Tracing of Inflammatory Intestinal Organoids via Computational Clearing.Nanomaterials (Basel, Switzerland) · 2026Article
- L-Citrulline Improves Recovery of Enterocytes While Not Affecting Gut Microbiota in an In Vitro Model of Chemotherapy-Induced Gastrointestinal Mucositis.Biomedicines · 2025Article
- Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing.Cancer medicine · 2024Article
- Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
- Mucositis and Infection in Hematology Patients.International journal of molecular sciences · 2023Article
- Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy.Cell death & disease · 2023Article
- The Protective Effects of Nutraceutical Components in Methotrexate-Induced Toxicity Models-An Overview.Microorganisms · 2022Review
- Gut Microbiota-Derived Short-Chain Fatty Acids: Impact on Cancer Treatment Response and Toxicities.Microorganisms · 2022Review
- Review
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Gastrointestinal mucositis is a complication of anticancer treatment, with few validated in vitro systems suitable to study the complex mechanisms of mucosal injury. Therefore, we aimed to develop and characterize a chemotherapeutic-induced model of mucositis using 3D intestinal organoids. Organoids derived from mouse ileum were grown for 7 days and incubated with different concentrations of the chemotherapeutic agent methotrexate (MTX). Metabolic activity, citrulline levels and cytokine/chemokine production were measured to determine the optimal dosage and incubation time. The protective effects of folinic acid on the toxicity of MTX were investigated by pre-treating organoids with (0.0005-50 µg/mL) folinic acid. The impact of microbial-derived short-chain fatty acids was evaluated by supplementation with butyrate in the organoid model. MTX caused a dose-dependent reduction in cell metabolic activity and citrulline production that was salvaged by folinic acid treatment. Overall, MTX causes significant organoid damage, which can be reversed upon removal of MTX. The protective effect of folinic acid suggest that the organoids respond in a clinical relevant manner. By using the model for intervention, it was found that prophylactic treatment with butyrate might be a valuable strategy for prophylactic mucositis prevention.
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