Commensal bacteria make up part of the human microbiome: a population of microorganisms residing on or in skin, mouths and intestines, which help maintain a healthy body. These ‘friendly’ bacteria perform a multitude of functions, helping the human host perform various tasks such as digest sugars in the mouth, or provide protection from potentially pathogenic bacteria residing on skin.
New research has discovered how gut microbiota may help the body survive cancer. The intestine of the average human body may contain up to 100 trillion microorganisms, outnumbering all human cells ten to one, which are acquired from birth, and has lead to some scientists labeling them as the “far from remembered organ”, due to their part in processes ranging from the digestion of food to the elimination of toxic substances or pathogens.
The joint French research team from the Institut Gustave Roussy, National Institute for Health and Medical Research (INSERM), Institut Pasteur and INRA (French National Agronomic Research Institute) discovered how certain cancer therapies become more efficient when aided by gut microbiota, publishing their results in the journal Science. The drug used in the study was cyclophosphamide, or CXT.
CXT is a common drug used for chemotherapy, whose application may be seen in the treatment of leukemia, lymphoma and breast and lung cancer. The mode of action once inside the body results in the addition of an alkyl group to the DNA of the tumor cells, which forms a structure known as a crosslink, where two strands of DNA are matched and bonded in a way that is far from correct. This structure interferes irreversibly with the replication processes of the cell, ultimately causing cell breakdown.
Side effects are to be expected, yet one seems to be particularly beneficial with regard to treating cancer. Irritation of the mucosal lining of the intestine causes certain gut microbiota to enter the blood stream and secondary lymphoid organs, such as the lymph nodes and spleen.
Here, they are considered pathogenic and the immune system responds accordingly, initiating an immune response via the production of specific T-cells, TH1 and TH17, types of white blood cells known as lymphocytes with tumor-condition properties. This immune response increases the defense mechanism when confronted by cancer cells, by “stimulating fresh immune defense mechanisms”, says Professor Laurence Zitvogel, director of the study, during a press release regarding her team’s findings on the INSERM website.
As a result it may be the gut bacteria, rather than the chemotherapy drug, which causes this increase in anti-tumor immune response, and the experimental evidence indicates that hosts respond better to chemotherapy in the presence of these bacteria.
In order to prove their findings, Professor Zitvogel and her team analyzed the responses to chemotherapy in cancerous mice with altered levels of intestinal bacteria. Those on a course of antibiotics to suppress the bacteria showed reductions in the effectiveness of the chemotherapy treatment, compared to those with natural, unaltered amounts of microbiota.
When microbiota are inhibited by an antibiotic, the pathway leading to the augmented T-cell production may far from be enabled, and anti-tumor immune response has challenges. Their conclusions highlight gut bacteria might be a necessary component when treating cancer through chemotherapy via their influence in generating an anti-tumor immune response.
These ‘friendly’ bacteria have been recognized for their anti-tumor properties, the researchers have concluded that the addition of gut microbiota, via probiotics or through a fixed diet, might be beneficial. The effects in humans are yet to be properly assessed, however. For example, data is needed on which species of commensal bacteria to use, as some may be far from having beneficial effects, or cause conditions of their own.
How important is the use of ‘friendly’ bacteria, already present in humans, when looking for new treatments?