Our gut microbiome, packed with bacteria, fungi, archaea and viruses, is a complex ecosystem and lives symbiotically within us, the microbiome’s human hosts. There are numerous studies that have demonstrated that our microbiome plays a fundamental role in our overall health and provides many physiological functions for us, that our own cells cannot provide. Whilst it provides structural, functional and metabolic functions including signalling networking, providing nutrients and immune system functions, each person’s gut microbiome is different, even in identical twins, and is dependent on lifestyle, diet, physiology and genetic make-up.
Whilst the microbiome is shaped during childbirth and childhood, our diet is a huge part of how it develops further into childhood and adulthood. Different foods can make changes in the gut microbiota resulting in a difference in the composition and metabolic activity. These changes can have an impact on health and how disease develops[i]. Our microbiome, therefore, has a key role in our immune system and maintaining this delicate ecosystem is critical to maintaining good health.
There are many demonstrations of how our immune system is controlled by our microbiome. For example, Bifidobacterium, which are often found in our guts, upregulate the activity of antigen presenting cells, APC. These APC cells help B and T cells in the immune system to recognise threats like tumours or viruses and respond to them. However, our immune system requires balance so it doesn’t over-react. There is a natural checkpoint for T cells which prevents them from recognising every cell as a threat. Cancer cells can take advantage of this mechanism and can shut down T cell activity before they have dealt with the threat.
Encouraging the growth of different protective strains of Bifidobacteria has the potential to treat or prevent cancers and other diseases. A therapy has been developed to improve the activity of T cells and prevent tumour cells from blocking the T cell checkpoint – this has been proven to be effective in only 25% – 35% of melanoma, skin cancer, cases. However, a recent study found that supplementing this antibody therapy with a Bifidobacteria supplement increased the number of APC cells[ii]. This has the potential to totally change the way that we treat cancer.
An out of balance microbiome often increases inflammation; beneficial bacteria usually provide anti-inflammatory properties whilst pathogenic ones often promote inflammation. Inflammation is a large risk factor for cancer development as it increases the risk of DNA damage and with it, the chance of normal tissue becoming malignant[iii]. The microbiome’s metabolites can directly act on the gut epithelial cells and can either promote carcinogenesis such as with hydrogen sulphide or Bacteroides fragilis toxin or prevent tumourgenesis as short term fatty acids like butyrate[iv]. Butyrate can change gene expresson in our cells by epigenetic regulation and also has anti-inflammatory properties[v] so this has the potential for many different therapeutic uses.
It’s not just colon cancer which can be influenced by the gut microbiome changes but it has also been linked to other cancers such as liver[vi] and breast[vii] cancer, possibly by a range of metabolic pathways. There are many mechanisms which may increase cancer progression but diet and exercise also play their part in maintaining our gut microbiome. Eating more fruit and vegetables increases the amount of dietary fibre consumed, which promotes healthy gut microbiome and modifies our metabolism in many ways. Dietary fibre decreases time of carcinogens in contact with gut wall whilst fermentation of some non-digestible matter by our microbiome creates metabolites that can prevent cancer. Eating as wide a range of fruits and vegetables helps increase the variety of different organisms in our microbiome and thereby, the variety of beneficial bacteria and their metabolites.
Whilst here are many initial studies which demonstrate that gut bacteria may be the key to preventing and potentially even curing cancer, it is still early days in this field of research. As the gut microbiome is so varied and complex, we cannot pinpoint whether certain bacteria are more important for health than others. Genetic mapping of our microbiome and may help us to see which bacteria we are missing and how we might supplement in these future in the form of probiotics and synbiotics. But given that the different microorganisms interact with each other, the ecosystem and balance might be most important. At the moment, evidence suggests increasing the variety and amounts of fruits and vegetables that we eat, eating more fermented and probiotic foods and eating more seasonally, like the Japanese diet which is thought to be a gold standard diet to increase the diversity of gut bacteria. High fat and alcohol diets should be avoided along with antibiotics, wherever possible as this decreases the diversity of our microbiome. There is so much yet to learn about the gut microbiome, but rest assured, we will find many benefits to improving our gut health!
[i] P. B. Eckburg, E. M. Bik, C. N. Bernstein et al., “Microbiology: diversity of the human intestinal microbial flora,” Science, vol. 308, no. 5728, pp. 1635–1638, 2005.
[ii] A. Sivan and L. Corrales et al. “Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.” Science 350.6264 (2015): 1084-089.
[iii] Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13:321–335
[iv] Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12:661–672
[v] Roberto Berni Canani, Margherita Di Costanzo, Ludovica Leone. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice Clinical EpigeneticsThe official journal of the Clinical Epigenetics Society20124:4
[vi] Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499:97–101
[vii] 11. Xuan C, Shamonki JM, Chung A, Dinome ML, Chung M, Sieling PA, Lee DJ. Microbial dysbiosis is associated with human breast cancer. PLOS One