ArticleCancer chemotherapy and pharmacology2021
Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- GutBlood neoplasia · 2025Trial
- Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra.Scientific reports · 2022Trial
- Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.Journal of neuroinflammation · 2026Article
- Fluoroquinolone Prophylaxis Uncovers High Prevalence Rates of Fluoroquinolone-ResistantCancers · 2026Article
- L-Citrulline Improves Recovery of Enterocytes While Not Affecting Gut Microbiota in an In Vitro Model of Chemotherapy-Induced Gastrointestinal Mucositis.Biomedicines · 2025Article
- Interplay between bile acids, gut microbiota, and the tumor immune microenvironment: mechanistic insights and therapeutic strategies.Frontiers in immunology · 2025Review
- Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of autologous stem cell transplantation in multiple myeloma.Scientific reports · 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
- Application of big data analyses to compare the impact of oral and gastrointestinal mucositis on risks and outcomes of febrile neutropenia and septicemia among patients hospitalized for the treatment of leukemia or multiple myeloma.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023Article
- A Gut Instinct on Leukaemia: A New Mechanistic Hypothesis for Microbiota-Immune Crosstalk in Disease Progression and Relapse.Microorganisms · 2022Review
- The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma.Frontiers in immunology · 2022Review
- Does Chemotherapy-Induced Gastrointestinal Mucositis Affect the Bioavailability and Efficacy of Anti-Infective Drugs?Biomedicines · 2021Review
- Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeConditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury.
methodsMale Wistar rats were treated with 4-8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation.
resultsMelphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms.
conclusionWe developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success.
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