Does the cure for cancer lie in the gut?

Could a faecal transplant save your life? This is the new line of research being pursued by an increasing number of cancer specialists around the world, as scientists attempt to find new ways to utilise the microbiome – the vast colony of micro-organisms that live within our gut – to tackle deadly diseases.

Last month, scientists at King’s College London (KCL) published the largest study so far showing that patients with the skin cancer melanoma were much more likely to respond to life-saving immunotherapy if their microbiomes contained certain healthy bacterial species.

It was a particularly landmark finding, as oncologists have long been seeking ways to boost treatment responses in melanoma patients, an aggressive cancer that can prove fatal if it spreads to other organs. While immunotherapies such as immune checkpoint inhibitors can stop melanoma in its tracks, they only work in less than 50 per cent of patients.

The gut has long been pigeonholed as a digestive organ, but in recent years scientists have begun to realise that it plays just as prominent a role in keeping our immune system ticking over. There are an estimated 100,000 billion bacteria, viruses and fungi living in our intestines, which we acquire very early in life. The composition of our microbiome then changes continuously throughout our lifetimes based on our diet, and other factors such as antibiotic exposure, sleep and stress.

While scientists are still figuring out the plethora of interactions that takes place between all these microbes, certain species of bacteria such as Bifidobacterium pseudocatenulatum or Akkermansia muciniphila have been associated with a better immune response.

According to Megan Rossi, who researches gut health at KCL, the microbiome holds vast potential for improving cancer treatment.

“We know that around 70 per cent of our immune system is located in our gut,” she says. “The gut microbes are very important in regulating the immune system, and studies out there are starting to show that. It’s looking like we can predict who will respond to different therapies based on the types of microbes they have in their gut.”

Some scientists have already taken tentative steps towards seeing whether we can improve the odds of successful treatment by directly modulating the microbiomes of cancer patients. While a probiotic containing certain healthy bacteria is not sufficient for doing this – Rossi describes this as a mere “drop in the ocean” – some researchers have already enjoyed limited success through conducting faecal transplants.

This involves taking stool samples from a healthy individual and transplanting that faecal matter into the gut of a cancer patient via a colonoscopy. The advantage is that it transfers an entire community of microbes and their synergistic interactions in one go.

Last year, oncologists at the National Cancer Institute in the US conducted a pilot study where they took fecal samples from melanoma patients who had responded to immunotherapy, and transplanted them into melanoma patients who were proving resistant. Six of the 15 resistant patients started to respond after receiving the transplant.

“It didn’t work for everyone, but they’re now doing more studies and trying to find out why those people started to respond, and the others still didn’t,” says Rossi.

Such is the interest in faecal transplantation that Rossi says her colleagues at KCL are currently working to identify so-called ‘super donors’, whose stool samples contain a particularly healthy composition of microbes, which could then be used to help chronically ill patients. “They screen healthy participants, checking for any kind of viral illnesses, go through their medical history, and then also look at their diet, how they sleep and cope with stress,” she says.

Rossi cautions that this research is still in its infancy in the cancer world – it is more advanced for treating conditions such as inflammatory bowel syndrome – and many more trials need to be done to investigate more, but she envisions a future in which faecal pills from super donors could be used in place of transplants, to boost response rates.

In years to come, we may even be able to specifically target harmful carcinogenic bacteria and eliminate them from the microbiomes of cancer patients, as a way of halting disease progression. Sequencing studies have identified a class of bacteria called Fusobacterium as being enriched in colorectal cancer tissues with the Fusobacterium nucleatum species implicated in both the growth of tumours and resistance to chemotherapy.

“That’s another area of research underway,” says Rossi. “People are looking at using phage therapy, viruses that target specific kinds of bacteria, as a way of removing bacteria which are more likely to promote cancer formation.”

But in the near future, Rossi predicts that it is more likely that we will begin to see cancer patients being triaged based on their microbiome. “Some patients may get a certain type of drug because they’ve got certain types of bacteria,” she says.

The microbiome may also provide a valuable way of picking up cancers at a very early stage by screening for tell-tale signatures of gut microbes and their metabolites – the chemicals produced by bacteria – which are found to be associated with different tumours.

Last week, scientists at the Spanish National Cancer Research Centre published a study in which they identified a distinct pattern of gut bacteria, fungi and viruses with pancreatic cancer. This was particularly notable because pancreatic cancer is often missed in the earliest stages, when it may be more treatable, because patients do not tend to be symptomatic until it is at an advanced stage.

“There’s definitely potential for identifying microbiome signatures because, with cancer, the earlier you catch it, the better the treatments are,” says Stephen Robinson, a cancer researcher at the University of East Anglia (UEA).

Robinson is currently involved in a collaboration with researchers from the Quadram Institute and the Norfolk and Norwich University Hospital to see whether a similar microbiome signature can be identified for breast cancer patients.

However, he cautions that it will likely take at least a decade before scientists can be confident that they have found a robust pattern which definitely signals the onset of the disease. “This involves long-term studies,” he says. “You need a large cohort of women who you then follow over the course of many years, to see whether there is a signature associated with the development of breast cancer.”

The project also has a more short-term goal that could assist with the treatment of current breast cancer sufferers. Robinson is particularly interested in observing the impact of different cancer therapies on the microbiomes of patients, to see whether there is any way of improving outcomes.

“We want to take them early on, before they begin treatments, and then see whether we can supplement them with particular members of the microbiota that might be beneficial, and make them respond better to chemotherapy or radiotherapy,” he says. “I think that’s where this research is going to be more immediately useful.”

But as the evidence continues to accumulate about the role which our gut health plays in our susceptibility to disease, how can all of us ensure that we have a healthier microbiome?

Rossi says that the answer is simple, ensuring that you get sufficient sleep and eat a greater variety of plant-based foods.

“Getting seven to nine hours of sleep a night is key, but so is eating more plants, and more diverse plants, which feeds the different species of bacteria,” she says. “I think that’s something we don’t do very well in the UK. We kind of stick to the same things, but there’s actually six different varieties of plants, from wholegrains to nuts, seeds, fruit, vegetables and spices. 

“People who enjoy all six have better gut health than those who eat the same type of plants. The next time you’re having a salad, add some grains, beans and pulses to it, to improve gut diversity.”

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