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

• Published in: Scientific reports 2020-06, Vol.10 (1), p.9094, Article 9094
• Main Authors: Pensec, Cindy, Gillaizeau, Florence, Guenot, Dominique, Bessard, Anne, Carton, Thomas, Leuillet, Sébastien, Campone, Mario, Neunlist, Michel, Blottière, Hervé M., Le Vacon, Françoise
• Format: Article
• Language: English
• Subjects: 13/21; 13/51; 38/23; 38/47; 38/91; 45/77; 631/326/2565/2142; 631/67/1612/1350; 64/60; Animal models; Animals; Antineoplastic Agents - adverse effects; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - microbiology; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Colon; Cytokines; Digestive system; Disease Models, Animal; Female; Gastrointestinal Microbiome; Gastrointestinal tract; Heterografts; Humanities and Social Sciences; Immunodeficiency; Inflammation; Intestinal microflora; Intestinal Mucosa - drug effects; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Intestine; Life Sciences; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - microbiology; Lung Neoplasms - pathology; Lung transplantation; Medication; Mice, SCID; Microbiology and Parasitology; Microbiota; multidisciplinary; Neoplasm Transplantation; Non-small cell lung carcinoma; Pemetrexed - adverse effects; Permeability; Pharmaceutical sciences; Relative abundance; Science; Science (multidisciplinary); Side effects; Small cell lung carcinoma; Specific Pathogen-Free Organisms; Toxicity; Tumors; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-65792-6

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.