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How a soup made with bacteria could boost your chances of beating cancer

By RACHEL ELLIS

AS RICHARD JONES prepared for a stem cell transplant to treat his cancer two years ago, he was offered a new and unusual treatment. Tests showed that his gut was colonised with antibiotic-resistant bacteria, putting him at ‘very high risk’ of a serious blood infection.

This is common among those who have had multiple courses of antibiotics (including cancer patients); while life-saving for infections these drugs also wipe out ‘good’ bacteria in the gut, allowing antibiotic-resistant bugs to thrive.

This meant that although a stem cell transplant to treat Richard’s leukaemia — which involves replacing damaged blood cells with healthy ones from a donor — had an 80 per cent chance of being successful, an infection afterwards could be fatal.

So his doctors asked if he wanted to try an experimental treatment — colloquially known as ‘Chinese soup’ — which, they hoped, would not only stop the drug-resistant bacteria from causing an infection, but also help him recover from cancer and minimise the chance of it returning. The ‘ soup’ was filled with good bacteria extracted from the poop of a healthy, screened donor.

Known medically as a faecal microbiota transplant (FMT), it’s an approach that’s becoming increasingly common for cancer patients — it’s also available in pill form.

(It was first used in China in the 4th century, hence its nickname Chinese soup.)

Richard was one of 20 patients (11 had cancer, nine had repeated urinary tract infections) given FMT as part of a trial at Imperial College London.

‘It wasn’t a particularly pleasant experience,’ he recalls. ‘I had an enema to clear out my system first, then a large tube was put up my nose and down into my tummy — and the “soup” was passed through it,’ says Richard, 62, who is married with two grown-up children (he’s asked to remain anonymous as many people don’t know about his illness).

‘But it was over very quickly and after the transplant I was able to fight off any infections I got, and I am now in remission for the cancer,’ adds Richard, who works in the media and lives in the South east.

Whether it was this treatment that made the difference is difficult to prove.

But it seems more than a coincidence as all the cancer patients who had a FMT in the same study were less likely to get serious blood infections, less likely to need antibiotics for hard-to-treat infections and spent less time in hospital, according to results published in the journal Clinical Infectious Diseases in 2020.

And 12 months after the stem cell transplant, 70 per cent of those who had the FMT were alive, whereas usually 36 per cent with that same level of disease survive, according to a separate analysis published in the journal Frontiers in Cellular and Infection Microbiology in 2021.

THE microbiome — the community of microbes in the body — is now widely accepted as being closely linked to gut conditions, including persistent bacterial infections, such as C. difficile.

And, increasingly, research is exploring the link between the gut microbiome and cancer to both prevent and treat most types of the disease, from skin and blood to prostate and kidney cancers.

‘Cancer occurs when rogue cells mutate and, when they start to multiply, the immune system doesn’t spot and stop them,’ explains Dr James Kinross, a microbiome scientist and colorectal consultant surgeon at Imperial College London.

‘ The more diverse the gut microbiome, the better the immune cells are at distinguishing between harmful and harmless bacteria — and this reduces the chance of cancer developing,’ he adds.

Yet many people’s microbiome is not up to scratch.

‘By the age of five, the microbiome has matured to an adult construct, but at this point it is assaulted with bad Western foods, pollutants and other factors which cause inflammation,’ explains Dr Kinross. ‘The microbiome simply can’t cope and doesn’t produce enough anti-inflammatory molecules to prevent the harmful consequences of these.

‘This process carries on for 20 to 30 years, and at some point a cancer is initiated because of this inflammation. This may explain why bowel cancer is becoming more common in young people.’

Of course, other factors contribute to cancer risk, including a family history, stress and poor sleep. equally, a well-balanced gut microbiome can help prevent cancer.

‘The microbiome is critical in explaining why a healthy diet is important for cancer prevention and treatment,’ says Dr Kinross, who was involved in a study, published in the journal Nature

Communications in 2015, which backed this up.

In the study, 20 African-Americans, who normally had a high-fat, low-fibre Western diet, and 20 rural Africans, who had a high-fibre, lowfat food intake, swapped diets.

After two weeks, those on the low-fat, high-fibre diet had lower levels of cancer biomarkers and associated changes to their gut microbiome, than those on the Western diet.

Your microbiome doesn’t only influence your cancer risk — it also affects the outcome of treatment.

‘Yet it is surprising how few oncologists understand how diet and the microbiome interfere with treatment,’ says Dr Kinross.

Blood cancer patients often have an especially poor gut microbiome. ‘This is because they tend to receive strong chemotherapy, which has side- effects of mouth ulcers and gut inflammation, so their nutrition might be poor,’ explains Dr Ben Mullish, a clinical lecturer at Imperial College London.

‘And — given that blood cancers weaken the immune system even more than other forms of cancer — these patients have particularly high rates of infections and require frequent antibiotics.

‘Many of them end up colonised with antibiotic-resistant bacteria, which not only prevent cancer treatments from working well, but also increase the risk of serious infections.’

Following the success of the trial Richard took part in, Imperial announced a new study in collaboration with biotech company enteroBiotix, involving 50 blood cancer patients who need a stem cell transplant: before this treatment, half will be given an FMT (in pill form) and half will have a placebo pill.

The theory is that the FMT will flood the gut with ‘beneficial’ bacteria that knocks out or at least suppresses drug-resistant bugs in the gut. These healthy bacteria also ‘boost’ the immune system so that the stem cell transplant works better, minimising the chance of the cancer coming back.

‘The results we have seen so far suggest changing the gut microbiome can make a big difference to the outcome; a kind of prehabilitation,’ says Dr Mullish.

Research is also examining how to engineer the microbiome to boost the effectiveness of cancer treatments such as chemotherapy and check-point inhibitors — a type of immunotherapy that blocks pro proteins that stop the immune system from attacking the cancer cells.

‘Studies show that the state of the gut microbes at the beginning of treatment is the biggest predictor of how long a patient survives,’ says Tim Spector, a professor of genetic epidemiology at King’s College London. A study he was involved in, with around 200 patients, found that those with advanced melanoma (skin cancer), who had poor gut health at the beginning of treatment were three times more likely to die or relapse in the year after treatment than those with good gut health.

The researchers found that three bacteria ( Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila) seemed to be associated with a better immune response, Nature Medicine reported last year.

Meanwhile, in a U.S. study, 15 patients with skin cancer in whom all treatments had failed (including a type of immunotherapy called anti-PD-1 or pembrolizumab) were given an FMT from patients who had responded well to anti-PD-1 treatment.

RESULTS, published in the journal Science in 2021, showed that this ‘changed the gut microbiome’ and subsequent anti-PD-1 treatment was effective, even in patients who had never responded to the treatment before.

‘ The microbiome is really important in how these drugs work because it holds the key to the immune system,’ says Dr Kinross.

‘Wherever cancer forms in the body, the tumour develops its own immune microbiome — a specific ecosystem of bugs around it, and they are incredibly important in determining how that cancer behaves: whether it is aggressive and how it responds to treatment.

‘If you modify this microbiome, it could potentially alter the course of the cancer. All cancers could benefit because they all have their own inherent microbiome.’

What does this all mean for us now? In terms of prevention, there are simple things we can all do to strengthen our microbiomes and reduce our cancer risk:

EAT less processed food because it causes inflammation.

INCREASE the amount of fibre and fermented foods containing good bacteria such as kefir.

ONLY use antibiotics and other drugs such as proton pump inhibitors (used for heartburn, which change acidity levels in the gut, potentially damaging the gut bacteria) when you really need them.

CONSIDeR taking a probiotic supplement. The theory is that they reintroduce good bacteria into the gut.

And telling cancer patients

about the importance of diet and the microbiome is vital, says Professor Spector.

‘ In some of the big cancer centres in the U.S., every patient will give a stool sample as part of their testing.

‘If they are having chemotherapy where they are killing off a lot of healthy cells, then once the treatment has finished they will have a transplant to put back their

own gut microbes that the chemo will have damaged.’

There are, of course, drawbacks. FMT donors must be screened to ensure they are infection-free, but there have been cases where recipients have died after picking up an infection from a donor.

The challenge with the gut microbiome is that ‘it’s really complicated, highly individualised and dynamic — the make-up of it shifts with you over time and it changes with each

cancer treatment,’ says Dr Kinross. And when introducing new communities of bacteria into someone, he adds: ‘We have to remember that if we get it wrong, there is the potential to cause harm.

‘For example, not all FMTs are the same and we may inadvertently make a cancer more likely to spread or increase the toxicity of drugs.’

Nevertheless, the promise of using the microbiome to prevent and treat cancer is huge.

GOOD HEALTH

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2023-03-28T07:00:00.0000000Z

2023-03-28T07:00:00.0000000Z

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