Gut Bacteria:  Both Friend and Foe

There are literally trillions of bacteria living within our intestines, where they have happily co-existed and evolved over many millennia. These gut bacteria, collectively known as the gut microbiota or microbiome, help us digest and metabolise food and other nutrients, as well as aid the breakdown of waste products.

Recently, new research has shown that gut bacteria play a much more important role in our general health and well-being than previously appreciated. It appears that gut bacteria influence how efficient our body’s immune system is at recognising and halting disease. In effect they serve as personal fitness trainers by keeping our immune cells primed and alert to the presence of harmful agents, whether these are bacteria, viruses, or damaged and dying cells within the body. As such there is evidence linking gut bacteria to a number of diverse ailments and diseases that include, depression, Parkinson disease, eczema, heart disease, irritable bowel, and obesity.

From a cancer perspective, it appears that the profile and balance of the different families of bacteria that reside in the gut significantly impact how well modern cancer immunotherapy drugs work. Cancer immunotherapy uses the body’s own immune system to target and destroy cancer cells and is a big new development in treating an increasing number of different cancers. However, some people seem to have a lower response to these forms of treatment than others. Whilst there are many reasons suggested for this, one exciting difference that is starting to emerge between those who respond to the treatment and those who don’t is the type and the diversity of bacteria in the patient’s gut.

Two recent groundbreaking studies have looked at this in more detail. The studies looked at the effect the gut bacteria had on the response of patients to a type of cancer immunotherapy called anti-PD1.  The one study led by Laurence Zitvogel at Gustave Roussy Cancer Centre, France, focused on non-small cell lung cancer and kidney cancer, while the other led by Jennifer Wargo at the MD Anderson Cancer, Texas, examined patients with metastatic melanoma.

 

 

For both studies, it was discovered that there was a strong correlation between the diversity of the gut bacteria and the response to immunotherapy. Additionally it appeared that certain types of bacteria, not just diversity alone, were associated with improved clinical outcome.  Remarkably, the French team noted that in some patients treated with anti-biotics, the cancers started to grow more rapidly as the effect of the immunotherapies became blunted. This was thought to occur as a result of a change in the gut microbiome induced by the antibiotics.

Kidney and lung cancer patients who responded well to cancer immunotherapy had a higher level of the bacterial phylum Firmucutes compared to non-responders. The best clinical outcome in both kidney and lung cancer patients was observed in those whose feaces had an abundance of the bacteria Akkermansia muciniphila. While lung cancer patients who failed to mount an immune response were found to have an under representation of Bifidobacterium.

Melanoma patients who displayed improved survival when treated in the same way, had a predominance of bacteria called Clostridiales, in particular a bacterium called Faecalibaterium. On the other hand, high numbers of Bacteriodales were found in patients who responded less well, suggesting these bacteria might be unfavourable.

While both fascinating and game-changing, these studies also raised several important questions – has the unnecessary, overuse of antibiotics led to a generation whose immune systems are less equipped to resist cancer?  Antibiotics are known to have profound effect on the gut bacteria, killing good as well as bad.  More research in this area will allow us to answer some of these uncertainties.

Loss of microbial diversity, known as dysbiosis, has long been associated with chronic health conditions. If bacteria appear to govern the body’s response to cancer though anti-cancer surveillance it may in future be possible to alter the composition of gut bacteria to help prevent/delay cancer, in addition to improving treatments.

A faecalibacterium – taken from: biofoundations.org

 

Leaky Gut Syndrome

As we have come to realise, not all bacteria in the gut are beneficial. In those with a leaky gut syndrome, bacteria may infiltrate the bowel wall more easily, where they can enter the general circulatory system. This causes inflammation and an increase in certain inflammatory markers.

Tumour cells then use these inflammatory markers to fuel their growth and progression. This is an example of how a leaky gut may trigger cellular changes increasing cancer risk.  Other causes of leaky gut include stress, toxins, certain food particles, drugs and organ malfunction, although not directly linked to cancer.

The laboratory of Professors Gallimore and Godkin, at Cardiff University are looking at bowel wall integrity, with a view to gaining a better understanding how chronic low-grade inflammation within the bowel wall may eventually lead to cancer.

Cancer Research Wales funded PhD student, Amanda Thomson, as part of her studies has recently managed to develop a leaky gut model for use in the laboratory. This could provide pioneering new research into gut permeability and may lead to the creation of ways to reduce gut leakiness – possibly through the modification of tiny passages between cells in the gut wall (known as tight junction proteins) in order to make the barrier stronger. Indeed, certain bacteria are now known to increase this leakiness.

 

Generating a Diverse and Favourable Gut Bacteria

How can one generate a diverse and favourable gut bacteria is the obvious question that falls from all this research,  with various strategies being mooted, such as use of prebiotic food substances, specific antibiotics that reduce harmful bacteria, and even faecal microbial transplantation. However, one relatively simple and risk-free way is a diet rich in fruit, vegetables and fibre, and low in processed foods.

While this may seem a familiar story and the same old health message – this time it appears to be playing to a different tune. We have long considered fruit and vegetables as a valuable source of anti-oxidants and vitamins – but their health benefits now appear to go much deeper. They seem to create the right biochemical environment within our intestines which allow ‘good’ bacteria to thrive.

At this stage, it has to be appreciated the benefits that various bacteria bring may not be universal to all diseases, only specific to some, such as cancer. And while this research is very much in its infancy, the recruitment of gut bacteria as an extra anti-cancer weapon is indeed, an exciting prospect.

Blog written by third year medical students, Lucy Armatage and Hester Lloyd-Cox who are supporting Cancer Research Wales as part of their studies.