Could gut bacteria be harnessed to fight cancer?

By Hudson Institute communications. Reviewed by Associate Professor Samuel Forster

Dr Samuel Forster researches the gut microbiome
Dr Samuel Forster

The gut microbiome, the vast ecosystem of bacteria that live within our digestive system, is becoming increasingly recognised for its essential role in supporting our physical and mental health. Now, two new studies from the US are showing that the composition of a patient’s gut bacteria could determine how likely they are to respond to cancer therapy.

One study (Gopalakrishnan et al) suggests that melanoma patients who responded to cancer immunotherapies had a more diverse gut microbiome which gave them greater immunity against tumours. Another paper (Routy et al) suggests antibiotics may strip the gut microbiome of bacteria that is essential for patients fighting advanced epithelial tumours.

Dr Samuel Forster, a researcher in Hudson Institute’s Centre for Innate Immunity and Infectious Diseases and the Wellcome Trust Sanger Institute in Cambridge, UK explains the findings – and whether we could prime our gut microbiome to help fight cancer.

How does gut bacteria affect cancer?

Between 100 and 1,000 bacterial species live within our gut and contribute to our health and wellbeing. You carry at least three times as many bacteria in our guts than cells in your bodies, but scientists are only beginning to understand the important health effects these bacteria may be having.

Immunotherapy is revolutionising the treatment of many previously untreatable cancers but some patients don’t respond and some encounter serious side effects. These patients are withdrawn from immunotherapy and miss out on access to potentially lifesaving treatment.

Scientists now think the mixture of bacteria within a person’s gut microbiome may determine both the effectiveness of immunotherapy in fighting cancer and how likely it is that they will experience side effects.

How do these results build on our understanding of the microbiome and cancer?

Image of gut microbiome and cancer
Photo: Jonathan Bailey, National Human Genome Research Institute. Link: https://flic.kr/p/He4Jbg

While it was previously clear that gut microbiota played an important role in a patient’s response to cancer immunotherapy, these results provide some important insights into how and why this occurs.

Low bacterial diversity in the gut is generally associated with poor health or medical treatments such as antibiotic use. The more species of bacteria found in the gut, the better the chance that a patient will carry beneficial bacteria that enhance the effectiveness of certain treatments.

Most studies in this area have shown a correlation or an association between particular types of gut bacteria and a particular disease, such as cancer.

These two studies are different in that they actually demonstrate in pre-clinical models that particular bacterial communities are having a direct effect, by stimulating the immune system in a way that improves outcomes of cancer treatment. Some types of gut bacteria seem to act like a vaccine adjuvant which boosts the immune system to make the vaccine (or in this case, the cancer treatment) work better.

How does gut bacteria research affect cancer treatment?

Importantly Routy et al. identify and experimentally validate an individual species of gut bacteria with significant potential for cancer treatment. Patients could potentially be screened for these species of gut bacteria prior to treatment or have the species introduced (for example, through faecal microbiota transplants) as part of their therapy.

The understanding of gut microbiota is still hampered by the limited number of bacterial species we have grown in the laboratory and genome sequenced. One key aim of our research is to overcome these barriers by growing the bacteria and making them available to researchers all over the world.

We still know comparatively little about the majority of bacteria that live in our guts. While 95 per cent of bacteria don’t have the ability to cause disease, most research focuses on the less than five per cent that do. Much more research is still required to understand how these bacteria might impact upon our health before we can develop therapies for broad application in cancer patients.

What is this going to mean for immunotherapy?

We are already seeing genetic testing being used to choose the most appropriate treatments for patients undergoing cancer therapy.

As our knowledge of gut bacteria increases, you can imagine a day when we will not only test patients, but even optimise the bacterial communities within their guts, to improve the success of cancer immunotherapy and other treatments.

Journal | Science

Title | Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

View publication | https://doi.org/10.1126/science.aan4236

Journal | Science

Title | Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

View publication | https://doi.org/10.1126/science.aan3706

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