What’s your microbiome got to do with cancer?

Award-winning medical journalist Jerome Burne Investigates

 

After you have been diagnosed with cancer, you will normally have a chat with an oncologist about treatment.  What drugs or drug combination you’ll get, when the course will start, and possibly a mention of side-effects.

If you ask about diet, you’ll most likely be told not to worry, eat anything, just get enough carbohydrates to keep your energy up. But this advice is changing fast. Ignoring the potential benefits of a change of diet looks like the last thing you need to do.

One of the leading researchers in the new field is a genetics professor at Kings College London Tim Spector. Two years ago, he was an author on a paper that made a detailed case for the importance of the microbiome, the large community of microbes that live in our gut, when treating cancer.

‘Although the research is new and ongoing,’ says Spector ‘we already know that gut bacteria play a highly important role in our health and the current epidemics of obesity, diabetes, allergy and even depression.

His paper had nothing to say about high or low fat or sugar or refined carbs, instead it focused on feeding and supporting the microbiome. The result was a protocol for patients to follow that would be completely alien to most oncologists and completely new for all but the most nutritionally aware patients.

The Key Points from the Research

These were the key points

*Both clinicians and patients should be careful to protect the microbiome.

**Patients should eat a diet that comes from a large variety of plants and contains proteins and dietary fibre

*They should, as far as possible, avoid two very widely used drugs – antibiotics and the PPIs (proton pump inhibitors) that block stomach acid – which could make cancer treatment less effective because of their damaging effect on gut bacteria.

*Patients should discuss their diet and what their microbiome needs with a nutritionist before and after conventional treatment.

This dietary advice would be challenging for many. Cut right back on meat from animals and eat large amount of plant material; aim for more than more than 30 types of plant every week!

The key benefit of this wide variety of plant species is that they would give you a lot of fibre – over 30gms – which is what gut bacteria thrive on. It gets turned into a bacterial food knows as SCFA – short chain fatty acids. If your bacteria are getting a good supply of SFCAs, that boosts your chance of responding well to standard cancer treatments.

Something else the microbiome would welcome, said Spector, was fermented foods, such as kefir and kimchee that contain gut-friendly bacteria.

Cancer Drugs – Checkpoint Inhibitors and Bacteria in the Microbiome

Interest in the role of the microbiome in cancer exploded several years ago as the result of a problem with the new and very effective type of cancer drugs called ‘checkpoint inhibitors.’ The drawback was that they only worked for a relatively small number of patients. But why?

The reason, it turned out, could be found in the microbiome. ‘This came as a surprise to most gene-focused oncologists,’ says Mr James Kinross, a senior lecturer in surgery at Imperial College in London who is unusual in being very interested in the ways bacteria influence human metabolism during surgery.

‘Checkpoint inhibitors was only benefitting a small percentage of patients because their effect was being cancelled by the actions of a couple of strains of gut bacteria,’ he explains. ‘The drugs were designed to turn off a natural safety switch – the ‘checkpoint’- that is activated if an immune response becomes too strong.’

By turning the switch back on, the bacteria were making the drugs ineffective. The unresponsive patients were found to have a pair of bacteria that allowed the safety switch to stay on. Another pair ensured it stayed off.

This was a dramatic demonstration of the active role that the microbiome can play in response to drugs. Other examples of bacteria compensating for drug effects have turned up since.  Prostate cancer, for instance, is driven by testosterone, so patients are often given a drug to lower their testosterone.

But sometimes it has no effect, and the tumour continues growing. Recently it was found that bacteria in the guts can make testosterone and as levels dropped, the bacteria stepped in to replace it.

Cancer and the Environment

For years cancer has been seen as genetic disease, so treatment has been aimed at targeting cancer-promoting genes,’ says Kinross. ‘But as cancer rates have continued to rise,’ it’s clear the environment also plays a major part.  Changes in the environment directly affect the guts and not just food and nutrition but things such as how much stress we are under, sort of family we are in, pollution levels’

Ironically, what has allowed us to investigate the microbiome in detail are the tools developed to study genes. ‘Without them we couldn’t begin to make sense of this huge, complex ecosystems.,’ he continues.  As a result, bacteria are no longer regarded as parasites freeloading on our guts and best eradicated.

’Instead the relationship between us and our microbiome and its vast population is essential to nearly all aspects of human health. A better understanding of it won’t just improve cancer treatment, but many other conditions such as heart disease, diabetes and Alzheimer’s.

Your Unique Microbiome

Complicating matters enormously is that everybody’s microbiome is unique; it has its own fingerprint, so may react differently from others to different foods, drugs and lifestyle changes – sleep, stress and so. Professor Spector may have uncovered an example of this when he was doing a detailed study of the way pairs of identical twins responded to carbohydrates – in this case a brownie.

Often the response of each in a pair was very different, one might have a sharp rise in blood glucose, the other no change. They were genetically identical, so what was creating the difference? Although he didn’t identify it at the time, it could well have been a difference in the response of their guts.

‘The aim of the drug side of microbiome studies is to engineer the microbiome to remove blocks to a drug working safely and efficiently,’ he says. ‘This is what has already happened with an effective drug for colon cancer called irinotecan that blocks an enzyme needed for tissue growth, which includes cancer. But an unpleasant side effect was diarrhoea. This can be stopped by targeting the bacteria involved.

‘At the moment we know that food, surgery and drugs all affect the microbiome and that in turn can have an effect both good and bad on chemotherapy as well as the quality of life after surgery,’ says Kinross

‘But we can’t say that particular diet is beneficial or harmful because the trials haven’t taken account of way each microbiome responds to it. And it’s not just food that trigger various responses, the guts are also affected by many other things in the environment – pets, the family you are in, your work conditions.

So, if you give the same diet to a group of patients, which is the way trials are done, you can’t expect the same outcome for each of them’

But even though individual microbiomes can vary so much, making trials more unreliable, that doesn’t mean there is no way of telling what works and what doesn’t. Researchers can tract the broad effects of particular diets.

Processed Foods

The highly processed foods such as frozen fries and frozen pizza, as well as ostensibly healthy, low fat, low salt ready-meals that, according to a recent survey, make up 50% of the British diet are definitely bad news for our guts, according to New Scientist of June 2021 and it is what many cancer patients eat often. Ignoring it no long seems an option.

Ultra-processed foods are defined as being made using processes not normally found in the home, such as high-pressure fat, and containing high levels of additives and sweeteners.  A study that compared a group fed highly processed foods for four weeks with another fed unprocessed foods (calories, protein, fat, carbohydrates etc staying the same) found those on processed food put on nearly a kilo. Those in the whole food group – lost a kilo.

Like nearly all nutritional research to date there was no attention paid to the microbiome to identify what was going on, but senior researchers made a well-informed guess.

One identified two candidates for the poor performance of the processed group. According to Robert Lustig, an obesity researcher at the University of California San Francisco, the lack of fibre meant the bacteria in their guts weren’t able to turn it into short chain fatty acids (SCFA) which reduce inflammation in the body.

Another pair of candidates, said Spector, were the artificial additives – such as sweeteners and emulsifiers – that changed ecosystem of the gut, allowing bacteria to get into gut wall, causing inflammation. ‘The more artificial foods you have, the more difficulty your gut microbes have in digesting it,’ says Spector

Case Study on the Ketogenic Diet as Part of Cancer Treatment

A new focus on the role of the microbiome looks like putting a new spin on the long running battle between the supporters of carbs and fat. The low carbohydrate high fat Ketogenic diet is regarded by many nutritionists as an effective anticancer diet with benefits for the microbiome.

‘It is effective for weight loss and as a treatment for diabetes, both of which raise the risk of cancer and it lowers blood glucose which is one of the food sources for tumours, ‘says Dublin based nutritionist Patricia Daly who specialises in helping patients with cancer.

She was diagnosed with a tumour in the eye and began using the ketogenic diet as part of her treatment. ‘It’s obviously a horrible place to have it, she says ‘but there was an advantage. Because the eye is transparent, my doctors and I could see the cells around the tumour returning to normal on the diet.

The melanoma in my eye (19mm diameter) has been inactive (a necrotic mass) for almost 10 years. A tumour outside my eye, 6mm in diameter, completely disappeared without further treatment. Angiogenesis (cancer-supplying blood vessels) and oedema (swelling) reduced significantly within weeks of starting Keto, thereby avoiding chemotherapy with Avastin or having my eyeball scooped out.’

But it is the relatively large amounts of fat you can eat on the ketogenic diet that worries some experts. Also, that it lacks the fibre needed to feed the microbiome. Asked whether such a diet could support the microbiome, Professor Spector replied flatly: ‘There is no evidence that fat-based diets are good for gut health!’

Daly seemed surprised at Spector’s certainty. ‘I’d never give a definitive answer to a question like that. We still know so little about the complexities of the microbiome. It depends so much on each individual one. That’s why I look at all the fundamentals that someone builds their health on. It’s multi-dimensional and there will never be a study to “prove” one approach

‘My tumour responded badly to a plant-based diet. It went literally from nothing to 2 cm in 3 months. It’s impossible to make such generalised statements. Fatty acids such as olive oil and other monounsaturated fats and omega 3 all have very positive impacts on microbiome. Again, context is everything.’

Daly also pointed to a study in the International Journal of Molecular Science in June 2020 that states: Different types of (fatty acid) FA dietary intakes play a crucial role in modifying the composition of gut microbiota.

The Future Role of Nutrition in Cancer Treatment

Spector told ‘Good Health’ that; ‘Oncologists are finally talking about diet with patients. We have a paper in Nature coming out next week on immunotherapy and gut microbes. All oncologists should know about gut health to help their patients.’

It should make for some lively discussions if well informed nutritionists are invited to play a central role in planning treatments.

Implementing these change will take time. ‘The majority of cancer doctors don’t know much about what goes on in the guts, says Kinross. ‘They concentrate on cancer biology and genetics. There has not been enough robust research on the microbiome and diet to make them confident of making supporting it part of treatment. But patients want to have more control and diet is a way of allowing them that. Some oncologists are more understanding about that than others.’

Dr Carol Granger a nutritionist and microbiologist doesn’t believe we need to wait for the evidence that diet affects the way patients respond to immunotherapy. ‘We know that patients well-being improves with better nutritional intake, she says. Evidence should soon be coming in on the effectiveness of more targeted treatments such as faecal implants from healthy donors, prebiotics to feed our population of helpful microbes and prebiotics to keep up their numbers if necessary.

How to Keep Your Gut Healthy

Meanwhile her microbiome support package that focuses on keeping the gut wall healthy, is a good place to start; keeping the right stuff in and the wrong stuff out. Important for its maintenance is the mucus supplied by two species of bacteria Akkermansia and Bifidobacterium, which also damp down inflammation that can be a trigger for cancer. Akkermansia can also use the mucus to produce the short-chain fatty acids (SCFAs) bacteria need.

Eat whole unprocessed food – fruit, vegetables, nuts and seeds all of which are high in fibre –along with the like of oats, olive oil, oily fish mushrooms and apples for the pectin. Tinned versions of foods such as beans and tomatoes are fine.

Avoid highly processed foods, ones with more than five ingredients, on the label as they threaten the barrier. So do antibiotics, PPI drugs that lower stomach acid, alcohol and chemotherapy. There’s some evidence that the ketogenic diet can help to reduce chemotherapy damage.

Further Information

Digestpro – in the Patrick Holford Body range supports digestive health and is available from HOLFORDirect.