[This article is an outside contribution by Dr Patricia Lepage (INRA), co-author of the paper. For further references about the author, see the short bio hereunder]
Research jointly conducted by investigators at Institut Gustave Roussy, Inserm, Institut Pasteur and INRA (National Agronomic Research Institute) in France has led to a rather surprising discovery on the manner in which cancer chemotherapy treatments act more effectively with the help of the intestinal flora (also known as the intestinal microbiota). Researchers have shown that the efficacy of one of the molecules most often used in chemotherapy relies to an extent on its capacity to mobilise certain bacteria from the intestinal microbiota toward the bloodstream and lymph nodes. Once inside the lymph nodes, these bacteria stimulate fresh immune defences which then enhance the body’s ability to fight the malignant tumour.
Results of this work were published in the journal Science on 22 November 2013.
Cyclophosphamide is one of the most widely used drugs in chemotherapy. However, like any treatment, it involves side effects (inflammation of the mucosa etc.), and disrupts the normal balance of the intestinal microbiota. Certain bacteria (of the Gram group of bacteria) can pass the intestinal barrier and enter the bloodstream and lymph nodes.
These bacteria, once in the general circulation of the body, may be considered harmful, and the body generates an immune response.
Surprisingly, the immune response directed against these bacteria helps the patient to better fight his/her tumour, by stimulating fresh immune defence mechanism. More specifically, immunisation against bacteria leads to the recruitment of effector lymphocytes different to those mobilised by chemotherapy. Their role consists of helping anti-tumour lymphocytes to stem the growth of tumours.
To verify these observations in mice, researchers suppressed all Gram bacteria from their intestinal microbiota. Results showed that the efficacy of the chemotherapy was reduced. The researchers also suggest that some antibiotics used during chemotherapy may dramatically reduce populations of these Gram bacteria, and thus negate their beneficial effect.
Author’s bio :
Dr. Patricia Lepage, PhD, is Molecular Microbiologist Research Associate (CR1) within the team “Functionality of the Intestinal Ecosystem” of the MICALIS Institute (Food and Gut Microbiology for human Health) at the National Institute for Agronomic Research, INRA, Jouy-en-Josas, France. She did both her PhD and postdoctoral research on gut microbiota dysbiosis in inflammatory bowel diseases (PhD in Joël Dore´s group, UEPSD, Ecology and Physiology of the Digestive Tract, INRA, Jouy-en-Josas, France from 2003-2005 and Postdoc in Stefan Schreiber´s group, ICMB, Institute for Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany, from 2006-2008), with particular focus on the mucosa-associated microbiota and its crosstalk with the host. She has interest in the functional characterization of the human gut microbiome, and its disease-associated dysfunctions using multidisciplinary Omics approaches.