Image: The human microbiome. (Credit: the National Human Genome Research Institute on Flickr. Licensed under a CY BY-NC 2.0 license.)
It has long been known that within us reside multitudes of bacteria, viruses and fungi, collectively known as the ‘microbiota’. These tiny organisms are found in their trillions, inhabiting numerous crevices and cavities of the body – primarily in the digestive tract (99 per cent), but also the skin, mouth, and urinary and genital passages.
They are able to modulate our immune responses, affect our hormone levels and influence our nervous system. The interdependency between our microbes and our health should not be surprising, as humans and micro-organisms have been co-evolving together over tens of thousands of years.
In terms of DNA, each person is comprised of their own genes (the ‘human genome’) as well as the genes found within these organisms, the ‘microbiome’. Each person’s microbiome is unique to themselves, as a fingerprint would be.
In recent years, we have started to uncover the complex interplay between these microbes and their role in human health and disease. Emerging research speculates that a diverse range of conditions including obesity, inflammatory bowel disease, colon cancer, diabetes and even depression may be influenced by the microbiome.
By decoding the genes of these organisms, research is enabling us to understand the importance of the microbiome, not only to the causes of illness, but also to how a patient may respond to a particular treatment.
Harmless guests can be beneficial to us
There has been a shift in emphasis away from these ‘bugs’ being regarded as causes of infectious disease or simply harmless guests who set up home within us. We are now realising that they can be beneficial to us, as well as affecting our susceptibility to certain diseases.
A person’s microbiome is first acquired as an infant during passage through the birth canal, and further develops through intake of milk, weaning onto food and environmental exposures.
A stable and mature microbiome is established by the age of about three years, but can fluctuate throughout a lifetime, dependent on changes in diet, episodes of illness and medication such as antibiotics.
It is not only the specific types of organism that are important, but also their diversity and relative proportions.Each will be competing against the other to survive and thrive within their environment, and our immune system helps to shape which species are successful colonisers.
We have made great strides in understanding the biology of cancer, but increasingly it is the tumour environment and the immune system which has come into focus.
The link between infectious agents and cancer has been established for several tumour types, including Helicobacter pylori bacteria and gastric cancer, hepatitis viruses and liver cancer, human papillomavirus and cervical cancer, and Epstein-Barr virus as a cause of lymphoma.
Bacteria can influence cancer formation and progression
Given that we are continuously exposed to our own microbiome, it is unsurprising that it may affect our susceptibility to cancer.
Studies in which specific bacteria were introduced into the gut of germ-free mice (reared in a sterile environment), have shown that some species can influence cancer formation and progression.This occurs by a variety of means – triggering inflammation, changing the immune response, and affecting the expression of cancer-related genes.
It is well established that inflammation is important in the causation of bowel cancer, and the microbiome may be an important influence on this inflammation. Studies have shown that the microbiome of patients with cancer differs to those without.
And transferring gut bacteria (by transplanting its faeces) from a mouse with bowel cancer to a cancer-free mouse can induce tumour formation in the healthy mouse. This raises the question of whether certain types of bacteria can increase our risk of developing certain cancers, and whether this could be used to screen people at risk.
Positive responses to immunotherapy
A recent study in 112 patients with advanced melanoma found that the type and variety of bacteria in a patient’s gut influences how well they respond to immunotherapy.
Patients whose disease responded to immunotherapy had a highly diverse range of gut microbes and an abundance of particular species of bacteria. Scientists have also found that introducing specific bacteria into germ-free mice led to a reduction in colitis, a common side-effect of immunotherapy.
In another study of 249 patients with lung, kidney and bladder cancers, those who received antibiotics prior to or during immunotherapy had a higher risk of relapse and poorer survival than those who did not.
Looking at the patients who responded well to immunotherapy, they found a preponderance of a bacteria called Akkermansia municiphila, which resides in the lining of the bowel.
When this bacterium was introduced into the gut of germ-free mice, they had an improved response to immunotherapy. The evidence suggests that such bacteria help by stimulating immune cells to rally against the cancer.
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Where does this research lead us?
Could manipulating our microbiome alter our risk of developing certain diseases or improve the chances that treatment will be a success? Emerging evidence is intriguing, but although associations have been seen, there is no evidence of direct causation.
The causes of cancer and many other diseases are multifactorial, with numerous lifestyle factors to consider, and it is challenging to tease out the relative contribution made by our microbiome. It is debatable whether specific differences seen in the microbiomes of individuals are a cause or consequence of a disease.
It must be borne in mind that most studies to date have been in mice and not humans, so we still don’t know how the results will translate to people. One suggestion would be to monitor people’s microbiome over time to determine if there is a difference between those who develop cancer and those who do not.
This is certainly an exciting area of research, and it will provide a new dimension to ‘precision medicine’ if in the future we are able to adjust a person’s microbiome to optimise the effectiveness of a particular treatment or moderate the risk of disease.
With one in two people in the UK now likely to develop cancer in their lifetime, continued investigation of the microbiome is showing promise for cancer prevention strategies, improved treatment and fewer side-effects.
Dr Samantha Nimalasena is a Clinical Research Fellow in the Targeted Therapy Team of the Division of Radiotherapy and Imaging.
Learn more about the ICR's research into the human microbiome.
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