How our gut bacteria affect cancer risk and response to treatment

May 11, 2017 by Hannah Rose Wardill Rachel Jane Gibson, The Conversation
Each person’s unique gut microbiota composition is in continuous communication with the immune system. Credit:

The trillions of bacteria living in our gut (called the gut microbiota) can help determine our risk of cancer, as well as how we might respond to cancer treatment.

Each person's unique is in constant communication with their immune system. This ensures good can thrive in the body, while bad bacteria and foreign material are eradicated.

The gut microbiota is therefore critical to making sure the immune system is in the best possible state to fight diseases – from the flu, to serious ones like cancer.

Researchers are now exploring how your unique determine your cancer risk, and whether modifying its composition can control cancer progression and predict response to treatment.

Your gut microbiota

Everyone's gut microbiota is unique, much like a fingerprint. In the first few years of life, it is at its most malleable, reflecting factors that occur during birth.

For instance, babies born through caesarean section have been reported to have lower numbers of good bacteria and higher numbers of pathogenic (bad) bacteria, compared with babies born vaginally.

Similar patterns have been reported in formula-fed infants, compared to those who have been breastfed. This suggests exposure to bacteria through diet shapes the composition of the gut microbiota in early life.

We don't exactly know what these differences mean as a child grows. But it is understood infants delivered through caesarean section not only have different gut bacteria, but are also more likely to develop allergies and immune-related diseases like asthma.

Microbiota and cancer risk

The gut and immune system are closely linked. Just as our gut bacteria control our immune system, our immune system controls our gut bacteria. Research now suggests this interaction plays a significant role in determining cancer risk.

Mice lacking certain immune molecules that slow the immune response, called anti-inflammatory cytokines, have more bad bacteria in their gut. This means a strong immune response ensures bad bacteria do not overpopulate our guts.

These are also more susceptible to bowel cancer than those with sufficient numbers of anti-inflammatory cytokines. The heightened cancer risk can be transferred to normal mice through their faeces (poo). This involves collecting the poo from a donor mouse, in this case mice lacking anti-inflammatory cytokines, and feeding it to a recipient mouse.

Poo from the donor mouse is rich in bacteria that reflects their gut microbiota. The high-risk mice have a lot of bad bacteria in their poo. Once transferred to the recipient mouse, these new bacteria flourish in the gut changing the composition of the microbiota.

Research has shown when the new gut microbiota is established in the recipient mice, their risk of developing bowel cancer increases.

A recent study conducted in humans paralleled these results. It showed long-term antibiotic use increased the risk of bowel cancer.

Antibiotics are well known to disrupt the composition of the gut microbiota, just like the mice lacking anti-inflammatory cytokines, leading to more bad bacteria in the gut and an increased risk of bowel cancer.

Microbiota and chemotherapy

A review of research published in the journal Nature also points to the gut microbiota playing a role in how patients respond to chemotherapy. The review suggests the gut microbiota determines the effectiveness of chemotherapy in two ways: through activating , and through its interaction with the immune system.

These mechanisms have been best described in mice that lack a gut microbiota. Such mice, termed "germ-free" mice, are bred in completely sterile conditions. They are exposed to no external sources of bacteria and have no bacteria in any part of their body.

Research has shown that chemotherapy in germ-free mice is less effective than in normal mice, and their tumours grow at higher rates.

This may be because many chemotherapy drugs initiate an immune response that kills tumour cells through a process called inflammation. In this study, germ-free mice had lower levels of inflammatory markers in their tumours following chemotherapy, compared to normal mice.

This indicates that the communication between the gut bacteria and immune system is critical for .

Many chemotherapy drugs are delivered to the patient in an inactive form, which is then activated by special enzymes in the liver and directly by gut bacteria. Different levels of these liver enzymes determine how effective chemotherapy will be at killing tumour cells.

Germ-free mice have more liver enzymes responsible for detoxifying chemotherapy drugs compared to . They are therefore able to eliminate the chemotherapy from their system very quickly. This leaves less time for the chemotherapy to kill tumour cells and therefore regulates the efficacy of treatment.

Once again, these effects were reversed by faecal transfer from mice with a normal gut microbiota.

In contrast, mice that have high levels of bad bacteria in their gut have also been shown to over-activate some chemotherapy drugs. Although this is thought to increase the ability of chemotherapy drugs to kill tumour cells, it can also cause unnecessary side effects as many chemotherapy drugs are unable to differentiate between healthy and .

Gut microbiota and diarrhoea

The most common side effect of chemotherapy is diarrhoea. Chemotherapy-induced diarrhoea is acutely life threatening as it starves people of vital nutrients, making them susceptible to serious infection and death.

Like cancer development and treatment, diarrhoea is associated with changes in the gut . Our yet-to-be published research found high levels of Proteobacteria in the gut before chemotherapy resulted in worsened diarrhoea and exacerbated weight loss in mice.

This research supports growing evidence in human trials showing that the levels of gut bacteria in the poo of patients before they start cancer treatment predicts their likelihood of developing diarrhoea. Similar findings have also been shown in patients treated with radiotherapy.

Can we change things?

This research provides an opportunity to modify gut bacteria to optimise treatment outcomes. This could be in the form of poo transfer, probiotics or even something as simple as changing someone's diet.

And the ability to understand someone's risk, and modify it before chemotherapy starts, can ensure the perfect balance between chemotherapy response and toxicity is achieved.

Work is currently being performed in Adelaide to identify the specific bacteria that are critical in determining response. Once this has been achieved, methods of mitigating risk can be evaluated and translated to patients.

Explore further: Changes in gut microbiota after unhealthy diet may protect from metabolic disease

Related Stories

Changes in gut microbiota after unhealthy diet may protect from metabolic disease

March 17, 2017
An unhealthy diet changes the composition of the gut flora and it is generally assumed that this maladaptation called "dysbiosis" triggers disease. A study by Matteo Serino and his colleagues at the Université Paul Sabatier ...

Gut microbes contribute to age-associated inflammation, mouse study finds

April 12, 2017
Inflammation increases with age and is a strong risk factor for death in the elderly, but the underlying cause has not been clear. A study published April 12 in Cell Host & Microbe reveals that gut microbes are one of the ...

Gut bacteria may play a role in Alzheimer's disease

February 10, 2017
New research from Lund University in Sweden has shown that intestinal bacteria can accelerate the development of Alzheimer's disease. According to the researchers behind the study, the results open up the door to new opportunities ...

Immune cells support good gut bacteria in fight against harmful bacteria

April 21, 2015
An immune cell protein, ID2, is critical for the maintenance of healthy gut microbiota and helps these good bacteria fight off harmful bacteria, report scientists from the University of Chicago. The study, published in Immunity ...

Chemotherapy: When our intestinal bacteria provide reinforcement

November 22, 2013
Research jointly conducted by investigators at Institut Gustave Roussy, Inserm, Institut Pasteur and INRA (French National Agronomic Research Institute) has led to a rather surprising discovery on the manner in which cancer ...

Gut microorganisms may determine cancer treatment outcome

November 21, 2013
An intact population of microorganisms that derive food and benefit from other organisms living in the intestine is required for optimal response to cancer therapy, according to a mouse study by scientists at the National ...

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

LincRNAs identified in human fat tissue

June 21, 2018
A large team of researchers from the U.S. and China has succeeded in identifying a number of RNA fragments found in human fat tissue. In their paper published in the journal Science Translational Medicine the group describes ...

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Scientists solve the case of the missing subplate, with wide implications for brain science

June 21, 2018
The disappearance of an entire brain region should be cause for concern. Yet, for decades scientists have calmly maintained that one brain area, the subplate, simply vanishes during the course of human development. Recently, ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.