Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models

Autor: Hervé M. Blottière, Françoise Le Vacon, Cindy Pensec, Thomas Carton, Sébastien Leuillet, Mario Campone, Florence Gillaizeau, Anne Bessard, Michel Neunlist, Dominique Guenot
Přispěvatelé: Biofortis Mérieux NutriSciences [Saint-Herblain], IMODI Consortium, Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epidémiologie, University of Strasbourg, 3 avenue Molière, 67000 Strasbourg, France, The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French National Research Agency (ANR) IMODI Consortium, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by an ANRT subvention (CIFRE fellowship) and the IMODI Consortium., Bodescot, Myriam
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Lung Neoplasms
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
lcsh:Medicine
Mice
SCID
Gut flora
TOXICITY
Carcinoma
Non-Small-Cell Lung
Medicine
Intestinal Mucosa
lcsh:Science
0303 health sciences
Multidisciplinary
biology
CANCER
3. Good health
Specific Pathogen-Free Organisms
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Pemetrexed
OBESITY
Toxicity
BACTERIA
Heterografts
Female
medicine.symptom
medicine.drug
Tumor Graft
[SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Inflammation
Antineoplastic Agents
[SDV.CAN]Life Sciences [q-bio]/Cancer
digestive system
Article
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Carcinoma
Animals
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
030304 developmental biology
Chemotherapy
Intestinal permeability
030306 microbiology
business.industry
lcsh:R
medicine.disease
biology.organism_classification
Gastrointestinal Microbiome
Disease Models
Animal
Cancer research
FECAL MICROBIOTA
lcsh:Q
Metagenomics
business
Non-small-cell lung cancer
Neoplasm Transplantation
Zdroj: Scientific Reports
Scientific Reports, Nature Publishing Group, 2020, 10 (1), ⟨10.1038/s41598-020-65792-6⟩
Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.9094. ⟨10.1038/s41598-020-65792-6⟩
Scientific Reports, 2020, 10 (1), pp.9094. ⟨10.1038/s41598-020-65792-6⟩
ISSN: 2045-2322
Popis: Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota’s role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown. The objective of this study was to evaluate the impact of pemetrexed and the tumor graft on the gut microbiota composition in immunodeficient mice. The faecal microbiota composition was studied with metabarcoding before, 24-h and one week after treatment. The colon epithelial barrier integrity was evaluated by histological examination, intestinal permeability measurement, and selected cytokines quantification. The tumor graft induced some variations in the microbiota composition. Pemetrexed further increased the relative abundance of Enterobacteriaceae and 3 families from the Firmicutes phylum: Enterococcaceae, Lactobacillaceae and Streptococcaceae. Pemetrexed also significantly altered the epithelial barrier integrity, which was associated with early inflammation. This pilot study shows that the association of a lung tumor graft with pemetrexed causes an alteration in the microbiota composition. Such information increases our knowledge about the impact of chemotherapy on the microbiota, which could help to minimize side effects and improve therapeutic effectiveness in the future.
Databáze: OpenAIRE
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