Cancer & Microbiome

Science

Cancer & Microbiome: An Introduction

Posted on November 26, 2018  - By Jacki

Our bodies have nearly 100 trillion cells that do not belong to us, but rather to bacteria. The human microbiome is a combination of all of the microbes that live on the surface of our bodies and within our bodies. These bacteria, keep us healthy and encourage a thriving ecosystem within our bodies—promoting the development of our immune systems, and allowing our bodily functions to be carried out healthfully. The human microbiome, on average, contains nearly 1000 different strains. Bacteria rule us—for every 1 human gene, there is 1.3 microbial genes that define us[1,2]. To put this into perspective, individuals are more microbe than human and most of that microbiome exists within our gut. All along, we have been basing our medicine off of how to treat our own genes and our illness, without the significant recognition that these microbial genes, whose DNA works to define us, deserve. Recent extensive investigation, in the field of medicine has delved into just how these bacteria can so significantly influence our healths and consequently, disease.

The Human Microbiome Project (2008) was established to research the microbiome in relation to our health. This project is on the forefront of developing the research necessary, in order to propel microbial treatments for disease forward in the field. Due to this project, among other research, we know that the microbiome has both potentially harmful bacteria and beneficial bacteria[2]. Although most bacteria are symbiotic, some promote disease, as pathogens. The healthy microbiome allows both to live in coexistence, however, if unbalanced, these normal interactions are pushed to a halt and into ‘dysbiosis’. The cause of dysbiosis can be attributed to an infectious illness inflammation, antibiotics, pollution, other chemical treatments, or to a poor diet and to poor exercise. This unbalance facilitates our susceptibilities to disease.
A dysbiotic state has been observed across numerous studies in cancer patients - specifically time and time again with the development of colorectal cancer. There is also implication of the microbiome as etiology to numerous other forms of cancer, including pancreatic, laryngeal, gallbladder and esophageal—suggesting bacteria as potential biomarkers, or treatments for disease[73-76]. These studies have lead us to a deeper understanding of cancer in specific cases. There are cases which suggest specific strains of bacteria, as markers of specific cancers, if present in a patient. For instance, Helicobacter Pylori, serves as a biomarker of stomach cancer, when in overabundance. As more biomarkers for specific cancers are identified, the way to treat cancer surrounds ameliorating the unbalance of the specific bacterial biomarker rather than the killing of cancer cells. Studies investigating bacterial treatments are underway now, in their infantile states.

Evidence shows that a microbiome in balance or once rebalanced can work to prevent disease and encourage apoptosis, while discouraging the markers of disease—inflammation and proliferation. The idea is to manipulate the microbiome to prevent invasion by pathogens and the potential consequent results of disease. One study, which summarizes the ability to treat our microbiomes to ameliorate disease is a study where diet plays a role in potentially ameliorating cancer state, via a diet adaptation. For instance, this study found that rural Africans had lower risks of colorectal cancer(CRC) when compared to African Americans. These rural Africans exhibited increased butyrate levels and abundance of Prevotella, a healthier bacteria, when compared to African Americans who exhibited a higher abundance of the cancer-associated Bacteroides bacteria[81]. The rural Africans have a higher resistant starch diet, while the African Americans eat more meat and fats[100]. These dietary effects, luckily could be reversed in a short period of time through increasing the plant-fiber content in the African American study participants. After just two weeks, these participants had guts that resembled those of their healthier comparisons[81]. This study showed a promising quick reciprocal change in the unhealthy microbiomes of the African Americans through a controlled diet change. In this aspect, Bacteroides associated with colorectal cancer risk, as well as other cancer-associated mucosal biomarkers decreased, corresponding to a decreased cancer risk. As of now, the aforementioned and described understandings of the microbiome and how they relate to cancer development, risk and prevention, detail three main points. The first is that, any unhealthy habit in terms of food, exercise or stress, and any inflammation provoker, such as pathogen or bacterial invasion can result in dysbiosis. The second, that cancer is associated with dysbiotic microbiome state. Lastly, as detailed by this study, dysbiosis and the biomarkers of cancer risk can be disrupted through simple diet choices which include: consuming more plant polysaccharides, fibers, less meats and less fats[81].

Dietary choices can and do affect cancer and disease risk[81, 82, 101]. Due to findings which suggest that those with cancer display different bacterial microbiotas than those who are healthy, it is postulated that if returned to a healthier composition, individuals could alter disease state. Therefore, it is clear that beneficially altering the microbiome in those with cancer, and limiting negative contributions to the microbiome–in the future poses a potential new route of treating or understanding the disease. On the forefront of using the bacteria as personalized medicine, there are the ideas of being able to eradicate harmful species, to nourish beneficial species, to ingest more beneficial species in the form of probiotics, and to consume healthful foods that encourage a healthy immune strengthening microbial system. Beyond using diet to change the microbiome, this field is overturning modern medicine with potential microbial modulating therapies including probiotics, prebiotics, fecal microbiota transplant, and exercise. By investigating the microbiome and how it influences and is influenced by disease, medicine is being redefined as we know it. Many diseases, such as IBS, Obesity, Crohn’s, Autism, Dementia, and Cancer are now linked to a lack of balance in the microbiome. This new understanding of the microbial mechanisms behind disease development and cancer development have augmented the importance of figuring out ways to strategically manipulate the gut composition to improve our healths. The changing food system promotes dysbiosis—through agricultural changes, meat consumption and the use of pesticides and antibiotics, as well as the rise of convenience foods.
These changes are determining how we eat, yet, it is important to prevail and still increase our abundance of healthy microbes[81;98-99]. Just as we shape our microbiomes through food choices, the microbiota shapes our healths. Whether disease comes down to cellular interactions within our bodies, predispositions or environmental factors, an anti-inflammatory diet remains the least harmful way we can individually control ourselves and our microbes most effectively, while within a significant degree of safety. There is still a need for many more human studies with longer follow up times and larger sample sizes to further our understanding of the microbiomes role in health. This paper further details the current studies which investigate the microbiome as it relates to cancer, the underlying mechanisms behind the relationship, what this means for medicine and how to individualistically take action to establish a flourishing, diverse microbiome.

Coming Soon:
1. Human Microbiome: What Is It?
In this section the human microbiome is discussed in brief. This includes, discussion of what the human microbiome is, and the significance as it pertains to medicine and health today.

2. History of the Microbiome: Why It Matters in the Sphere of Public Health
This section details how the idea of the microbiome came to be in relation to determining disease. This includes the history of microbiology, and discoveries of the microbiome. This section also details why speak on the microbiome is even important in the sphere of public health.

3. A Microbiome in Dysbiosis: The Proposed Mechanisms Dismantling Our Healths
This section details dysbiosis and the mechanisms behind dysbiosis. This details our current state of globalization, and the microbial mechanisms causing disease. This section brings about the mechanisms behind disease in general, and begins the discussion on the microbiome-cancer discourse.

4. The Microbiome and Cancer
This section details how the microbiome, or particularly dysbiosis, impacts and influences cancer. This section speaks on the specific mechanisms of microbes in encouraging cancer. This section details the individual strains associated with cancer.

5. The Future of Bacteria as Medicine: Specific to Cancer
This section details how understanding the microbiome is engaging new ways of treating disease. This section discusses diet in brief, probiotics, FMTs, and the ideas of manipulating the microbiome for disease treatment and prevention. This section mainly details these possibilities as they pertain to cancer.

6. The Diet: Our Greatest Control
This section further details the mention of diet spread throughout the other sections. This section details how diet is our only individual control to impactfully manipulate our microbiome, to prevent disease or further health degradation, with the greatest amount of safety.

Sources:
1. “The Microbiome.” The Nutrition Source, 24 Aug. 2017.
2. The NIH HMP Working Group, Peterson J, Garges S, et al. The NIH Human Microbiome Project. Genome Research. 2009;19(12):2317-2323.
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76. Sharma V, Chauhan VS, Nath G, Kumar A, Shukla VK. Role of bile bacteria in gallbladder carcinoma. Hepato-gastroenterology. 2007; 54(78):1622..
81.O'Keefe SJ, Li JV, Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015;6:6342. Published 2015 Apr 28
82. Xie G, Zhang S, Zheng X, Jia W. Metabolomics approaches for characterizing metabolic interactions between host and its commensal microbes. Electrophoresis. 2013; 34(19):2787–2798.
98. V.E. Wagner, N. Dey, J. Guruge, A. Hsiao, P.P. Ahern, N.P. Semenkovich, J.I. Gordon, Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition, Sci. Transl. Med. (2016) a164
99. F M. Wu, N.P. McNulty, D.A. Rodionov, M.S. Khoroshkin, N.W. Griffin, J. Cheng, J.I. Gordon, Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides, Science (2015) ac5992
100. O'Keefe SJ, Chung D, Mahmoud N, Sepulveda AR, Manafe M, Arch J, Adada H, van der Merwe T. Why do African Americans get more colon cancer than Native Africans? The Journal of nutrition. 2007; 137(1):175S–182S