Chemotherapy‐driven dysbiosis in the intestinal microbiome

Alimentary Pharmacology and Therapeutics - Tập 42 Số 5 - Trang 515-528 - 2015
Emmanuel Montassier1,2, Thomas Gastinne3, Pajau Vangay4, Gabriel A. Al‐Ghalith4,1, Stanislas Bruley des Varannes5, Sébastien Massart6, Philippe Moreau3, G. Potel2, Marie France De La Cochetiere7, Éric Batard2, Dan Knights8,1
1Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA
2EA 3826 Thérapeutiques Cliniques et Expérimentales des Infections Faculté de Médecine Université de Nantes Nantes France
3Department of hematology, Nantes University Hospital, Nantes, France
4Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN, USA
5Institut des Maladies de l’Appareil Digestif, Nantes University Hospital, Nantes, France
6Gembloux Agro‐Bio Tech University of Liège Gembloux Belgium
7EA 3826 Thérapeutiques Cliniques et Expérimentales des Infections Faculté de Médecine INSERM Université de Nantes Nantes France
8BioTechnology Institute, University of Minnesota, St. Paul, MN, USA

Tóm tắt

SummaryBackgroundChemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome.AimTo identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high‐throughput DNA‐sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy.MethodsWe amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non‐Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics.ResultsWe found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P = 0.0002) and Actinobacteria (P = 0.002) and significant increases in abundances of Proteobacteria (P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P = 0.0001), energy metabolism (P = 0.001), metabolism of cofactors and vitamins (P = 0.006), and increased capacity for glycan metabolism (P = 0.0002), signal transduction (P = 0.0002) and xenobiotics biodegradation (P = 0.002).ConclusionsOur study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy‐induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome‐targeted interventions in cancer patients.

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Alimentary Pharmacology and Therapeutics

Tập 42 Số 5

515-528

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