Could the microbiome help us stop cancer before it starts? 

By Sophie Wedekind and Sydney Ghazarian

We often think of cancer risk as something shaped by our genes. But scientists have known for decades that it isn't written in our DNA alone. There are also more dynamic things at play – and one of the most important ones is the microbiome.

This community of tiny organisms, which lives mainly in the gut, helps us digest food, supports our immune system and protects against disease. And as it does so, it’s constantly adapting and adjusting to our changing conditions, inside and out.

Scientists have already shown that the microbiome is crucial for our overall health. Now they’re beginning to uncover how important it can be for preventing cancer, particularly in people at risk of developing it at younger ages. 

In this article, we’re highlighting how our pioneering research is revealing the complex web of interactions between the microbiome and the body. In time, these projects could give us more precise ways to protect people from cancer.

What is the microbiome?

The microbiome is made up of trillions of microscopic organisms called microbes, which come from hundreds of different families of bacteria, fungi and viruses. There are actually more of these tiny hitchhikers in your body than your own cells, and the community they form is as unique as your fingerprint.

Genetics, the environment and lifestyle all play a part in shaping someone's microbiome. It's important to keep it in balance, as the right mix of beneficial and harmless microbes can stop potentially damaging ones from causing problems. Some of the best ways to support it are by eating a healthy diet, stopping smoking and cutting down on alcohol.

The early years of the microbiome

Everyone's microbiome starts developing from the moment they're born. It can change quickly over the first few years of life as infants encounter microbes for the first time, but after that it mostly settles down. So, no matter how old someone is, you can probably trace their unique combination of microbes back to their early childhood.  

It’s hard to define exactly what makes a microbiome healthy, but researchers agree that overall, a diverse mix of microbes is better. That's largely because it can help the body’s defences (the immune system) tell friend from foe and respond appropriately.

This matters right from the beginning. Professor Sir Mel Greaves, a Cancer Research UK-funded researcher at the Institute of Cancer Research (ICR) in London, has found important associations between a less diverse microbiome, a more jumpy immune system, and a type of childhood blood cancer called acute lymphoblastic leukaemia (ALL). 

Over more than 30 years of research, Greaves identified that a small number of children are born with a DNA change linked to ALL, but very few of them go on to develop the disease. Those that do may be at higher risk because of their microbiome.

The evidence so far suggests that if children with ALL-linked gene changes aren’t exposed to diverse microbes in infancy, their immune system could be more likely to overreact to common infections when they’re slightly older, potentially triggering other changes that can contribute to ALL.

Greaves and his team are now testing that idea in mice. Over time, they want to pinpoint exactly which bugs are important for priming the immune system and see if giving them to mice with ALL linked-gene changes can stop the disease before it starts. 

Those experiments could eventually make it possible to prevent some forms of ALL, the most common cancer in children, by boosting the microbiome with special diets or probiotics.

“That’s an ambitious long-term goal for us,” Greaves told Cancer News in 2024. “As a researcher, I think about the many families who have been affected by ALL. And even though it’s becoming more treatable, the side effects can still be incredibly difficult. Focusing on prevention means not only minimising these side effects but saving lives altogether. That’s what we’re striving for.” 

Ageing, the microbiome and cancer risk

Although the microbiome is relatively stable after early childhood, it can begin to change in more profound ways as people reach their later years.

Another Cancer Research UK-funded researcher, Professor Filipe Cabreiro from Imperial College London, has been working to understand what these changes are and what they can mean for cancer.

“As we grow older, the microbiome starts to change quite noticeably,” he explains. “Some microbes, which are usually kept under control, begin to grow in much larger numbers, while others start to disappear. The microbial community reshapes, but what it actually means for our health isn’t yet fully clear.” 

What is becoming clear is that these shifts aren’t random. Cabreiro has found that they seem to be tied to one of the most fundamental processes in biology: how our cells produce and use energy.

When we’re young, our bodies have huge energy demands, and the microbiome helps meet them by breaking down food into energy we can use. "But as we get older,” Cabreiro explains, “our cells become less efficient at processing that energy. This can lead to a build-up of harmful by-products, which we think may contribute to the development of cancer.”  

Cabreiro and his team are now testing that theory. In the lab, they’re examining the by-products that come from different combinations of microbes and investigating whether specific ones increase the likelihood that mouse models will develop bowel cancer.  

“One of the big challenges in microbiome research is moving beyond associations and proving cause and effect,” he says. “We want to understand whether specific by-products made by microbes can actually drive cancer development, because that could open the door to predicting risk and potentially preventing the disease.”  

There are still lots of open questions, but Cabreiro thinks it should be possible to work with the microbiome to reduce people's risk of bowel cancer.  

“We could specifically target microbes that are overproducing harmful molecules, or we could add other microbes to mop those molecules up,” he explains. “This is the beauty with microbes – nothing is ever wasted. The product of one gets used by something else. Sometimes you don't have that something else, but we can introduce it artificially.”

Ageing, the microbiome and cancer risk

Although the microbiome is relatively stable after early childhood, it can begin to change in more profound ways as people reach their later years.

Another Cancer Research UK-funded researcher, Professor Filipe Cabreiro from Imperial College London, has been working to understand what these changes are and what they can mean for cancer.

“As we grow older, the microbiome starts to change quite noticeably,” he explains. “Some microbes, which are usually kept under control, begin to grow in much larger numbers, while others start to disappear. The microbial community reshapes, but what it actually means for our health isn’t yet fully clear.” 

What is becoming clear is that these shifts aren’t random. Cabreiro has found that they seem to be tied to one of the most fundamental processes in biology: how our cells produce and use energy.

When we’re young, our bodies have huge energy demands, and the microbiome helps meet them by breaking down food into energy we can use. "But as we get older,” Cabreiro explains, “our cells become less efficient at processing that energy. This can lead to a build-up of harmful by-products, which we think may contribute to the development of cancer.”  

Cabreiro and his team are now testing that theory. In the lab, they’re examining the by-products that come from different combinations of microbes and investigating whether specific ones increase the likelihood that mouse models will develop bowel cancer.  

“One of the big challenges in microbiome research is moving beyond associations and proving cause and effect,” he says. “We want to understand whether specific by-products made by microbes can actually drive cancer development, because that could open the door to predicting risk and potentially preventing the disease.”  

There are still lots of open questions, but Cabreiro thinks it should be possible to work with the microbiome to reduce people's risk of bowel cancer.  

“We could specifically target microbes that are overproducing harmful molecules, or we could add other microbes to mop those molecules up,” he explains. “This is the beauty with microbes – nothing is ever wasted. The product of one gets used by something else. Sometimes you don't have that something else, but we can introduce it artificially.”

The microbiome and early-onset cancer

Although he's focusing on ageing, Cabreiro thinks there’s potential for microbiome research to make a difference for younger adults, too. Early-onset cancers (when cancers associated with old age are diagnosed in under-50s) are on the rise, and looking at the microbiome could help us understand why. 

“What we’re seeing can’t be explained by genetics alone,” says Cabreiro. “These shifts are happening far too quickly. It points our attention to environmental factors and the microbiome, which sits at the interface between the outside world and our biology."

That has some profound implications.

“We’re living in very different conditions, with different environmental pressures than previous generations, and there's a growing sense that we may be ageing faster. If that’s true, it could explain why we’re seeing more disease at younger ages and why we need to start thinking much earlier about prevention.” 

Although the microbiome is a complex web of interactions, there's already evidence that specific microbes could be playing an important role. 

Cancer Grand Challenges teams Mutographs and OPTIMISTICC have both found associations between a DNA-damaging toxin called colibactin, which is produced by a rare type of E. coli, and bowel cancer in younger adults.

It’s important to note that E. coli is a vital part of a healthy gut microbiome. However, when the microbiome falls out of balance, some harmful strains can become more common. These are the ones that produce colibactin.  

There’s much more research needed, but the findings suggest that colibactin is an important piece of the puzzle for understanding why the number of early-onset bowel cancers is increasing. With our funding, another team at the ICR is now trying to work out where it fits.

Led by Professor Trevor Graham, the team is using modern analysis tools to compare samples of bowel tumours taken over the past 100 years to see if they can spot any important differences.   

"Our leading idea is that there's a particular kind of E. coli that lives in the bowels of young people today that wasn't there in the past," Graham told the BBC earlier this year.

"If these so-called bad bugs are causing the increase, we should see the signature of these bad bugs, the damage, was rare in the past and becomes increasingly common as we move towards the present day,” he added. “We can also test other ideas too." 

The future of microbiome research

All this research has the potential to help predict and prevent more cancers, but there's still much more to learn about the microbiome. That's why team OPTIMISTICC has also been improving the tools scientists use to study it. 

Their work focuses on a tool called PathSeq, which scientists use to analyse DNA from the microbiome. The problem is, because the microbiome is so busy and diverse, actually spotting specific organisms in all the DNA data PathSeq produces can feel like the world’s hardest game of I Spy.

OPTIMISTICC has improved PathSeq by adding features that declutter the data it pulls out from a tissue sample. The programme can now help recognise and remove DNA sequences that can get in the way of analysis, such as DNA from human cells that can sometimes get mixed in.  

Already, these improvements are making a difference. When they tested the upgraded tool on DNA from thousands of tumour samples from UK’s 100,000 Genomes Project, OPTIMISTICC found new trends that could link specific microbes and certain tumour types. 

For example, in a small number of bowel cancers, as well as some head and neck cancers, the team found an unusual parasite called Trichamonas. The parasite is known for causing the sexually transmitted infection (STI) trichomoniasis, and this is the first time it’s been detected in these types of tumours. It’s not yet clear exactly how this parasite may be contributing to cancer, if it is at all, but the finding offers a new direction for future studies. 

The team also found that tumours with more mutations also tend to have more microbes in them, giving researchers a new way to think about the possible connections between the microbiome and how tumours develop.  

From risk to prevention

Research around the microbiome is as dynamic as the microbiome itself. On the one side, scientists are considering how the microbes in our gut can shape our health, like an unseen force acting behind the scenes. On the other, they’re treating it as a looking glass – a way to glimpse what else may be happening even deeper inside the body.  

From Cabreiro’s work linking microbial byproducts to cancer biology, to the discovery of DNA‑damaging toxins like colibactin, to OPTIMISTICC’s new tools for mapping microbes, scientists are beginning to piece together the mysteries of the microbiome. As they do so, their findings connect and build upon one another like a web, revealing patterns that no single study could uncover alone.   

The more we understand how the microbiome works – and how our bodies work with it – the more we can do to shift from treating cancer to preventing it, detecting risk earlier and changing the course of the disease before it has a chance to begin. 

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