Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models.
Cindy PensecFlorence GillaizeauDominique GuenotAnne BessardThomas CartonSébastien LeuilletMario CamponeMichel NeunlistHervé M BlottièreFrançoise Le VaconPublished in: Scientific reports (2020)
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.
Keyphrases
- small cell lung cancer
- advanced non small cell lung cancer
- oxidative stress
- locally advanced
- advanced cancer
- end stage renal disease
- palliative care
- healthcare
- randomized controlled trial
- newly diagnosed
- chronic kidney disease
- systematic review
- mouse model
- escherichia coli
- ejection fraction
- metabolic syndrome
- pseudomonas aeruginosa
- diabetic rats
- multidrug resistant
- squamous cell carcinoma
- case report
- type diabetes
- peritoneal dialysis
- drug induced
- current status
- patient reported
- high fat diet induced
- silver nanoparticles