Not all bacteria are created equal. They are a part of the one hundred trillion microorganisms that make up the gut microbiota and reside in the warm, nutrient-rich home of the human intestine. The gut microbiota is essential for processes like digestion and the development of the intestinal and extraintestinal components of the immune system. In the January 2015 issue of Science Translational Medicine, Lawrence Zitvogel and colleagues discuss the various advancements and accumulating evidence that continues to reveal the gut microbiota’s role in cancer.

A healthy composition of gut bacteria has effects that extend beyond the digestive system.

A healthy composition of gut bacteria has effects that extend beyond the digestive system.  The link between microbiota and cancer exists not only between colorectal cancer, but also for extraintestinal cancers, such as breast and hepatocellular carcinoma, a type of liver cancer. Dysbiosis, the microbial imbalance inside the body, can affect the onset of cancer, tumor progression, and even response to cancer therapy.

There are many influences that can impact the microbiota such as genetics, pathogenic organisms, aging, and environmental factors such as antibiotics, smoking, hormones, and diet. Epidemiological studies have shown that there is a relationship between dysbiosis and intestinal cancers. In addition, the by-products of the gut microbiota can target intestinal epithelial cells and elicit an inflammatory response, causing damage to the cells lining the small and large intestine.

The gut microbiota also affects and is affected by cancer treatments. Some therapies exert toxic effects on intestinal bacteria, sometimes leading to dysbiosis. Due to this effect, allogenic stem cell transplantation, the transfer of stem cells from a healthy donor to a patient following high-intensity radiation or chemotherapy, can be toxic to an individual’s microbiota. This relationship can also work the in opposite direction, as a bacterial imbalance can interfere with cancer treatments, inhibiting their efficacy. One example is the possibility that intestinal bacteria play a major role in the failure of allogenic stem cell transplantations by inducing acute graft-versus-host disease. When this happens, the immune cells in the transplanted tissue attack the host’s own body cells, a negative outcome of the treatment.

Beneficial dysbiosis induced by anticancer therapies may be required for, or at least improve the clinical efficacy of the treatment. A healthy gut microbiota may work with other treatments to elicit an immune response against malignant cells or attack tumors. In these cases, the bacteria conferred beneficial responses and aided in cancer treatments. However, a positive correlation is not always the case as bacteria can reduce the benefits of anticancer chemotherapy.

 Evidence has revealed that intestinal bacteria can impact cancer therapies by affecting immunological circuitries and therefore, tumor responses.

The reduction in benefit is detrimental dysbiosis, which increases treatment toxicity and limits the efficacy of the therapy.  Evidence has revealed that intestinal bacteria can impact cancer therapies by affecting immunological circuitries and therefore, tumor responses.  Lymphodepleting total body irradiation- suppressing an individual’s immune system to be more receptive of transplants- has been found to promote the translocation of parts of the microbiota across the intestinal epithelium. This process increases levels of blood-borne proinflamation cytokines which are proteins involved in cell signaling, and affects the efficacy of the adoptively transferred tumor-destroying T-cells.  

Since the microbiota plays such a key role in cancer onset, progression, and response to treatment, scientists are investigating manipulation of the gut microbe as a mode of cancer therapy. Antibiotics, probiotics, prebiotics, and postbiotics can all theoretically alter the composition of the gut, and therefore alter the effects of anticancer therapies. Antibiotics are chemicals with a preferential cytotoxicity for one or more bacterial species, often targeting different types of bacteria to stimulate dysbiosis. Some states of dysbiosis enhance chemotherapeutic agents, while others counteract them. It is possible that antibiotics may be used to reverse a state of detrimental dysbiosis; however, specificity in relation to what bacteria are targeted becomes an issue.

Results of animal tumor model studies of probiotics reveal that these living bacteria, or other microorganisms, may be able to prevent intestinal cancers.  In these models, researchers continue to study probiotics as vectors, as a means of introducing tumor-associated antigens, immunostimulatory molecules, or enzymes that reduce chemotherapy toxicity.  However, it has not been confirmed whether probiotics are safe and can evoke the appropriate immune response in humans. Additionally, investigation is on-going as to whether using probiotics to limit gastrointestinal toxicity of radiation and chemotherapies is beneficial.

Prebiotics are nondigestible compounds that stimulate the growth and/or functions of parts of the microbiota while postbiotics are nonviable bacterial products (products that will not grow and develop in order to function successfully) from probiotic microorganisms that impact biological activities in the host. These two routes have been entertained as possibilities to prevent cancer, although little research has been executed compared to the studies being conducted concerning antibiotics and probiotics.

Manipulating the gut microbiota may provide another angle that researchers can use to tackle the continuous cancer epidemic, by finding ways to limit tumor incidence and improve results of anticancer agents through the bacteria inside the human body.

Recent studies have revealed that intestinal bacteria influences not only oncogenesis, but also tumor development and even receptivity and efficiency of anticancer therapies. Manipulating the gut microbiota may provide another angle that researchers can use to tackle the continuous cancer epidemic, by finding ways to limit tumor incidence and improve results of anticancer agents through the bacteria inside the human body. There have been promising results in several models that use the gut microbiota to prevent cancer, but it has yet to be established in humans. In addition, selective manipulation of the gut bacteria to optimize clinical anticancer chemo-, radio-, or immunotherapies is a relatively new idea and more studies must take place in order to understand this innovative strategy and its value better.


REFERENCES

Zitvogel L et al. Cancer and the gut microbiota: An unexpected link. Science Translational Medicine. 21 January 2015. 7(271):1-4.

 

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