Our Unique Microbiome and Cancer

by Rosa Morena, PhD

What is the Microbiome?

Micro-organisms and their specific genetic material or genome, constitute the microbiome. Our microbiome is therefore defined by the genome of viruses, bacteria and fungi that may reside within our body at any given time1. Because the specific combination of micro-organisms is unique to each of us, our microbiome is equally unique.

It may be unacceptable for some, but micro-organisms are constant and normal residents of our skin, nose, mouth, digestive and reproductive systems. In fact, the great majority of micro-organisms that constitute our unique microbiome exist within our intestinal tract (2, 3). What benefits do they provide? For example, within the intestinal tract, micro-organisms, primarily bacteria, help in the processing of complex carbohydrates, providing us with nutrients and vitamins2. By colonizing the inner-surface of our intestines, micro-organisms protect us by effectively creating a physical barrier against harmful bugs. Additionally, gut-micro-organisms play essential roles in the development and strengthening of our immune system (2). Therefore, scientists believe that our unique normal gut-microbiota is critical for human health.

The Bad and the Good of our Microbiome in Cancer

By now you may be wondering, how bacteria in our gut are involved in cancer?  Gut-microbiota is not a static entity. It’s influenced by various factors including:  diet, age, drugs (e.g., antibiotics), environmental factors and infectious pathogens, among many others. When the gut-microbiota is negatively altered by any of these factors, symbiosis is affected; scientists refer to this altered-state as dysbiosis (2, 3). Increasing evidence supports that cancer and dysbiosis are promoted by similar factors2. Perhaps the best example is the development of colorectal cancer, where infections and antibiotic use may be implicated in the development of dysbiosis and subsequent carcinogenesis (2, 3, 4).

However, dysbiosis in the gut may have far reaching carcinogenic potential. Recent findings suggest that dysbiosis in gut-microbiota may exert long distance effects on the liver, inducing inflammation and contributing to the development of hepatocellular carcinoma (3, 5).

But not all is bad when talking about the microbiome and cancer. Interestingly, the gut-microbiota may exert important influences on the activity and toxicity of chemotherapeutic agents. Studies have shown that manipulating the activity of specific gut-bacterial enzymes may reduce the toxicity and improve the effectiveness of some chemotherapies (2, 6). For example, the drug Camptothecin (CT-11 or irinotecan), used in the treatment of colon cancer, is known to induce severe diarrhea, which limits its effectiveness. This unwanted side effect has been linked to the way Camptothecin is metabolized by intestinal microbiota (2, 6). Scientists have devised a strategy to specifically inhibit the bacterial enzyme responsible for this side effect, which should allow the use of greater doses of the drug (6).

Manipulating the Microbiome, is it possible?

Researchers are just beginning to recognize and understand the complex interactions that occur within our own bodies, with our natural and unique microbiota. Intestinal bacteria with their unique set of enzymes, able to metabolize different drugs, present the opportunity for manipulation to modulate toxicity and efficacy. Moreover, our microbiota may also be manipulated to improve effectiveness of cancer immunotherapy (2).

It is clear that dysbiosis or an unbalanced microbiota plays a role in carcinogenesis. Nevertheless, scientists also agree that the connection between dysbiosis and specific cancers in the human merits further study. Researchers believe that manipulating the microbiome may hold promise for the prevention and treatment of cancer. Some of the strategies that are envisioned include the use of antibiotics, probiotics, prebiotics, postbiotics and microbiota transplantation (2, 3).

Unfortunately, chemotherapy and radiotherapy have detrimental effects on the gut-microbiota, leading to dysbiosis (2, 7-9). Currently, strategies aimed at restoring a balanced gut-microbiota via microbiota transplantation are being considered for patients undergoing bone marrow transplantation (https://www.mskcc.org/blog/microbiome-studies-may-benefit-patients).

The uniqueness of our microbiome is likely to present a great challenge for the successful implementation of any of these strategies. Considering the great diversity of micro-organisms, and thus the great number of genes, a better understanding of the specific biological activities of these organisms is required. The National Institutes of Health sponsored a great initiative, aimed at understanding our microbiome’s intricacies. Through the Human Microbiome Project, an international collaborative effort, scientists have mapped the human microbiome in health and disease (https://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body). These studies are sure to propel great scientific applications that aim to harness the power of our microbiome for a healthier life.

References:

  1. Cénit MC, Matzaraki V, Tigchelaar EF & Zhernakova A (2014) ‘Rapidly expanding knowledge on the role of the gut microbiome in health and disease’. Biochim Biophys Acta.1842(10),1981-1992. doi: 10.1016/j.bbadis.2014.05.023.

  2. Zitvogel L, Galluzzi L, Viaud S, Vétizou M, Daillère R, Merad M & Kroemer G (2015) ‘Cancer and the gut microbiota: An unexpected link’. Science Translational Medicine 7(271), 1-4. DOI:10.1126/scitranslmed.3010473

  3. Schwabe RF & Jobin C (2013) ‘The microbiome and cancer’. Nat. Rev. Cancer 13, 800- 812.

  4. Wang JL, Chang CH, Lin JW, Wu LC, Chuang MS & Lai MS (2014) ‘Infection, antibiotic therapy and risk of colorectal cancer: A nationwide nested case–control study in patients with Type 2 diabetes mellitus’. Int. J. Cancer 135,956-967.

  5. Roderburg C & Luedde T (2014) ‘The role of the gut microbiome in the development and progression of liver cirrhosis and hepatocellular carcinoma’. J. Gut Microbes 5(4),441-445.

  6. Wallace, BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S & Redinbo MR (2010) ‘Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme’. Science 330(6005),831-835.

  7. Zwielehner J, Lassl C, Hippe B, Pointner A, Switzeny OJ, Remely M, Kitzweger E, Ruckser R & Haslberger AG (2011) ‘Changes in Human Fecal Microbiota Due to Chemotherapy Analyzed by TaqMan-PCR, 454 Sequencing and PCR-DGGE Fingerprinting’. PLOS One 6(12): e28654. doi:10.1371/journal.pone.0028654.

  8. Touchefeu Y, Montassier E, Nieman K, Gastinne T, Potel G, des Varanne SB, Le Vacon F & de La Cochetiere MF (2014)  ‘Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis – current evidence and potential clinical applications’.  Aliment. Pharmacol. Ther. 40,409-421.

  9. Nam YD, Kim HJ, Seo JG, Kang SW & Bae JW (2013) ‘Impact of Pelvic Radiotherapy on Gut Microbiota of Gynecological Cancer Patients Revealed by Massive Pyrosequencing’. PLOS One 8(12): e82659.

    doi:10.1371/journal.pone.0082659