C. PENSEC, T. CARTON, S. LEUILLET, D. GUENOT, IMODI Consortium, M. CAMPONE, H. BLOTTIERE, F. LE VACON
Despite significant progress in anti-cancer treatment such as immunotherapy, chemotherapy remains a gold standard. Pemetrexed is a chemotherapeutic agent commonly used in lung cancer. This drug has a broad-spectrum effect that can induce significant side effects in patients. We have previously shown for the first time that this drug has a strong impact on the gut microbiota composition in PDX models of lung adenocarcinoma. The aim of this new study was to explore the impact of pemetrexed on the gut microbiota and gastrointestinal inflammation in resistant and sensitive mice of our PDX.
Upon establishment of the PDX model, mice were treated with pemetrexed for 2 weeks. Stool specimens were collected at 3 time-points. Gut microbiota composition was studied by 16S rRNA gene sequencing and the taxonomic classification of sequences was obtained using an in-house bioinformatic pipeline based on mothur software. In parallel, body weight was recorded and tissues were sampled for assessment of toxicity and inflammation.
Pemetrexed induced a significant body weight loss after each treatment cycle reflecting toxicity as known in clinical results. A detailed analysis of the gut microbiota, intestinal permeability, and inflammation are underway. Preliminary analysis of the gut microbiota data shows an increase of Enterobacteriaceae and a decrease of Porphyromonadaceae.
A better understanding of gut microbiota alterations induced by chemotherapy could help reduce side effects. The microbiota represents an important additional “indicator” to evaluate the toxicity of pharmacological treatments that should be taken into account in the development of new molecules.
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Cindy Pensec receives a Microbiome Hero award for her PhD wich she is completing at the University of Nantes, France. For 2 years she has been working on human and mice microbiota to understand the impact of chemotherapies on the gut microbiota.