Cancer - is the cause and solution in the microbiome?

Cancer is one of the leading causes of mortality, accounting for nearly one in six deaths worldwide (1). Among several treatment options, chemotherapy and immunotherapy are used to treat cancer by preventing cancer cells from dividing or by boosting the immune system to eliminate cancer cells (2). Despite advances, treatment outcomes for most cancers are still unsatisfactory.

The gut microbiome, i.e. the totality of microorganisms living in the gut, is increasingly coming to the fore in cancer research. It is considered an important factor associated with both tumorigenesis and the efficacy of cancer therapies (3). Understanding how microorganisms affect cancer may open new avenues for cancer prevention, treatment, and management (8,9).

The gut microbiome has an impact on our health

The human body is a complex ecosystem inhabited and influenced by a plethora of microorganisms, including bacteria, yeast, fungi and viruses, which together form the microbiome. On average, a healthy human body consists of about 30 trillion cells and is inhabited by about 39 trillion bacterial cells (4). The microbiome influences a variety of metabolic processes, including the formation of hormones, essential vitamins, and other bioactive compounds that cannot be acquired by humans in any other way (5). The microbiome also has a direct influence on the immune and nervous systems (6).

Microbiome and the Connection of Cancer

Changes in the microbiome can contribute to the development of various diseases. In the context of cancer, it has been demonstrated that some specific bacteria are involved in the process of tumor development. In this process, some of these bacteria activate inflammatory reactions and disrupt the mucus layers that protect the body from external invaders. This causes an environment that promotes tumor growth. In other cases, bacteria also promote cancer survival by making cells resistant to anticancer drugs (7).

However, gut bacteria can also help fight tumors (12). In 2013, a study at the National Cancer Institute in Bethesda, Maryland, showed that some cancer treatments rely on the gut microbiome to activate the immune system. The chemotherapy drug cyclophosphamide was found to damage the mucus layer that lines the gut, allowing some gut bacteria to migrate to the lymph nodes and spleen, where they activate specific immune cells. In mice raised without gut microbes or treated with antibiotics, the drug largely lost its anticancer effect (13, 14).

The gut microbiome has the potential to influence the effectiveness of cancer therapy

In another study, stool samples from several cancer patients treated with chemotherapy or a combination of chemotherapy and immunotherapy were analyzed. It was found that the gut microbiome of those cancer patients who responded well to therapy had higher microbial diversity (10). Diversity describes the diversity of the microbiome and also indicates whether the different bacterial species are found evenly in the gut or whether some bacterial species dominate. The more different bacterial species are found evenly in the intestine, the higher the diversity and the more resistant the microbiome is in principle (11).

The relationship between gut microbiota and humans is complex. Each individual has inherited a specific microbiome footprint since birth. With aging, diet and lifestyle, the microbiome is constantly evolving and changing. If we already take a preventive approach to our microbiome health and positively influence the microbiome with the right diet and lifestyle, we take an important step towards a healthy life.

Refereneces

(1) World Health Organization. 2018. https://www.who.int/health-topics/cancer. Accessed 2019.

(2) Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015;3:436–43.

(3) Zitvogel L, Ma Y, Raoult D, Kroemer G, Gajewski TF. The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science. 2018;359:1366–70.

(4) Sender R, Fuchs S, Milo R. Revised estimates for the number of human and Bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533.

(5) Lepage P, Leclerc MC, Joossens M, Mondot S, Blottière HM, Raes J, et al. A metagenomic insight into our gut’s microbiome. Gut. 2013;62(1):146–58.

(6) Vernocchi P, Del Chierico F, Putignani L. Gut microbiota profiling: metabolomics based approach to unravel compounds affecting human health. Front Microbiol. 2016;7:1144.

(7) Zhang H, Sun L. When human cells meet bacteria: precision medicine for cancers using the microbiota. Am J Cancer Res. 2018;8(7):1157–75.

(8) Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084–9.

(9) Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015 Nov 27;350(6264):1079–84.

(10) Heshiki Y, Vazquez-Uribe R, Li J, Ni Y, Quainoo S, Imamovic L, Li J, Sørensen M, Chow BKC, Weiss GJ, Xu A, Sommer MOA, Panagiotou G (2020) Predictable modulation of cancer treatment outcomes by the gut microbiota. Microbiome 8(1):28. doi: 10.1186/s40168-020-00811-2.

(11) Lozupone CA, et al. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220 (2012).

(12) https://www.nature.com/news/gut-microbes-can-shape-responses-to-cancer-immunotherapy-1.22938

(13) https://science.sciencemag.org/content/342/6161/971

(14) https://science.sciencemag.org/content/342/6161/967