Gut Microbes: Beyond the Brain PT1 – Cancer

Gut microbes are well known for their surprising influence on the brain. The brain-gut-axis, first described less than 10 years ago, establishes the existence of a two-way communication highway between the brain and the gut. But the influence of gut microbes extends far and wide, well beyond our brain.

Gut microbes are important players in medical conditions like irritable bowel syndrome¹, a disease that affects one in five Australians. Obesity and diabetes are also influenced by the microbial composition of our gut². Even cancer and a patient’s response to some anti-cancer therapies can be influenced by gut microbes.

In this multi-part feature, we describe some of the most striking examples of how gut microbes affect our health, outside the brain. Here, we focus on how gut bacteria influences different types of cancer.

Gut Microbes, Beyond the brain – The Basics:

In recent years, multiple studies have reported convincing evidence of a link between gut microbes and the onset and progression of cancer, as well as a link with a patient’s response to anti-cancer therapies. Researchers are now talking about the so-called cancer microbiome³.

Studies using mouse models of cancer suggest that gut bacteria have a tumour-promoting effect on colorectal cancer, gastric cancer, liver cancer, lung cancer and breast cancer. Human based studies have also been conducted and associations have been established between our bacterial guests and conditions like gastric cancer, gastric MALT lymphoma, skin MALT lymphoma and ocular adnexal lymphoma, breast cancer, oesophaegal cancer, colorectal cancer, head and neck cancer, prostate cancer and pancreatic cancer^7-8.

How strong is the evidence surrounding gut microbes?

A classic example is Helicobacter pylori, a bacteria found in about half of the world population and in about 15% of all Australians⁴. The bacteria are known to cause gastritis, sometimes leading to peptic ulcers. However, recent studies now suggest that this bacterium can also cause some cancers, such as gastric adenocarcinoma⁵ or MALT lymphoma⁶, a rare cancer affecting mucosa-associated lymphoid tissue (MALT), which usually targets the stomach.

Another aspect of the cancer-microbe connection is response to therapy. Studies have shown that the microbiome has an important role in regulating the environment where cancer immunotherapy functions, particularly for checkpoint inhibitors. These are drugs that block the function of a special group of proteins used by cancer cells to evade the immune system. In a recent study, French researchers used mice and humans to show that a primary reason why checkpoint inhibitors fail to work may be due to an abnormal gut microbiome composition. They found that the presence of Akkermansia mucinophilia, a gut bacterium, had beneficial effects in the treatment of renal, urothelial and lung cancers⁹.  Another study, focused on melanoma patients, found a larger number of “good” bacteria in patients who responded positively to cancer immunotherapy, compared to patients who did not respond well to therapy¹⁰.

Implications for your gut microbe health

More research is needed to better understand exactly how bacteria can influence cancer and therapy effectiveness. The evidence so far, however, strongly supports an important role of these tiny inhabitants with different aspects of cancer development and treatment.

Future studies in this arena have a good chance of identifying microbiota-based therapeutic strategies to fight cancer. The use of prebiotics, probiotics or improved diet and microbiota transfers are some of the potential strategies that may help restore the health and balance of our gut, potentially alleviating cancer or helping with cancer treatment.

References

1. Mayer, E.A., Savidge, T. and Shulman, R.J., 2014. Brain–gut microbiome interactions and functional bowel disorders. Gastroenterology, 146(6), pp.1500-1512. Read it!
2. Patterson, E., Ryan, P.M., Cryan, J.F., Dinan, T.G., Ross, R.P., Fitzgerald, G.F. and Stanton, C., 2016. Gut microbiota, obesity and diabetes. Postgraduate Medical Journal, 92(1087), pp.286-300. Read it!
3. Pandeya, N., Whiteman, D.C. and Australian Cancer Study, 2011. Prevalence and determinants of Helicobacter pylori sero‐positivity in the Australian adult community. Journal of gastroenterology and hepatology, 26(8), pp.1283-1289. Read it!
4. Herrera, V. and Parsonnet, J., 2009. Helicobacter pylori and gastric adenocarcinoma. Clinical Microbiology and Infection, 15(11), pp.971-976. Read it!
5. Farinha, P. and Gascoyne, R.D., 2005. Helicobacter pylori and MALT lymphoma. Gastroenterology,128(6), pp.1579-1605. Read it!
6. Elinav, E., Garrett, W.S., Trinchieri, G. and Wargo, J., 2019. The cancer microbiome. Nature Reviews Cancer, p.1. Read it!
7. Goodman, B. and Gardner, H., 2018. The microbiome and cancer. The Journal of pathology,244(5), pp.667-676. Read it!
8. Schwabe, R.F. and Jobin, C., 2013. The microbiome and cancer. Nature Reviews Cancer, 13(11), p.800. Read it!
9. Routy, B., Le Chatelier, E., Derosa, L., Duong, C.P., Alou, M.T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M.P. and Fidelle, M., 2018. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, 359(6371), pp.91-97. Read it!
10. Gopalakrishnan, V., Spencer, C.N., Nezi, L., Reuben, A., Andrews, M.C., Karpinets, T.V., Prieto, P.A., Vicente, D., Hoffman, K., Wei, S.C. and Cogdill, A.P., 2018. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science, 359(6371), pp.97-103. Read it!