Bowel cancer may be caused by a common bacteria that damages DNA lining the gut and leaves a traceable ‘fingerprint’
- Scientists have shown a toxin released by a strain of E.coli can cause cancer
- The toxin, colibactin, causes unique patterns, or ‘fingerprints’, of DNA damage
- It can mutate and multiply in the cells of stomach lining and cause bowel cancer
A common type of gut bacteria may play a role in the development of bowel cancer, research suggests.
An international team of scientists have shown that a toxin released by a strain of E.coli – a dangerous bacteria usually found in the lower intestine – causes unique ‘fingerprints’ of DNA damage to the cells lining the gut.
These patterns were observed mainly in bowel cancer tumours, showing ‘a direct link’ between the microbial toxin and the genetic changes that drive cancer development.
The toxin in question is called colibactin and it can mutate and multiply in the cells of the stomach lining and cause bowel cancer, the second most deadly cancer in the UK.
Scientists have shown that a toxin released by a strain of E.coli – a bacteria usually found in lower intestine – causes unique patterns, or ‘fingerprints’, of DNA damage to cells lining the gut
Certain E.Coli strains residing in the human gut produce colibactin.
It is a small toxin that damages the genetic information within a cell causing mutations, which can lead to cancer.
However, colibactin’s chemical structure and the molecular mechanism underlying its genotoxic effects have remained unknown since it was first discovered in 2006.
Professor Hans Clevers and his team at the Hubrecht Institute in The Netherlands focused on one strain of E. coli producing colibactin, which is more often present in the stool samples of people with bowel cancer compared to healthy people.
Because colibactin can cause DNA damage in cells grown in the lab, they thought the toxin might be doing the same to cells lining the gut in humans.
The team used human intestinal organoids, or miniature replicas of the gut grown in the lab, and exposed them to colibactin-producing E. coli.
They analysed the DNA sequence of the gut cells in the mock up intestines after five months and found about double the DNA damage in them, compared to the dummies exposed to ‘regular’ E. coli that didn’t produce the colibactin.
The researchers also found that the DNA damage caused by colibactin followed two very specific patterns – like a fingerprint – which were unique to the toxin.
To determine whether the DNA damage caused by the bacteria played a role in bowel cancer, the researchers then analysed the DNA sequences of more than 5500 tumour samples from the UK and Netherlands, with the help of Dr Henry Wood and Professor Philip Quirke from the University of Leeds.
Over 40,000 Britons are diagnosed with bowel cancer yearly, and it’s the second-biggest cancer killer (file)
First, they checked for the two colibactin DNA damage fingerprints in over 3600 Dutch samples of various cancer types. The fingerprints were present in multiple tumours, and much more often in bowel cancers than other cancer types.
The researchers then refined their investigation on bowel cancer tumours specifically, and analysed over 2000 bowel cancer samples from the UK, collected as part of the 100,000 Genomes Project run by Genomics England.
Among these samples, the colibactin fingerprints were present in 4-5% of patients. This suggests that colibactin-producing E. coli may contribute to 1 in 20 bowel cancer cases in the UK.
Scientists said that other bacterial toxins from gut bacteria might have similar effects and the hunt for them is now on as researchers seek to determine whether this mechanism of DNA damage is widespread.
Understanding the early triggers that could lead to bowel cancer may help doctors prevent its development and detect it at its earliest stage, when treatment is most likely to be successful.
There are around 42,000 new bowel cancer cases in the UK every year.
Understanding the early triggers that could lead to bowel cancer may help doctors prevent its development and detect it at its earliest stage, when treatment is most likely to be successful.
What is bowel cancer and what are the symptoms?
Bowel cancer is a general term for cancer that begins in the large bowel. Depending on where the cancer starts, bowel cancer is sometimes called colon or rectal cancer.
Bowel cancer is one of the most common types of cancer diagnosed in the UK. Most people diagnosed with it are over the age of 60.
Symptoms of bowel cancer
The 3 main symptoms of bowel cancer are:
- persistent blood in your poo – that happens for no obvious reason or is associated with a change in bowel habit
- a persistent change in your bowel habit – which is usually having to poo more and your poo may also become more runny
- persistent lower abdominal (tummy) pain, bloating or discomfort – that’s always caused by eating and may be associated with loss of appetite or significant unintentional weight loss
Most people with these symptoms do not have bowel cancer. Other health problems can cause similar symptoms. For example:
- blood in the poo when associated with pain or soreness is more often caused by piles (haemorrhoids)
- a change in bowel habit or abdominal pain is usually caused by something you’ve eaten
- a change in bowel habit to going less often, with harder poo, is not usually caused by any serious condition – it may be worth trying laxatives before seeing your GP
These symptoms should be taken more seriously as you get older and when they persist despite simple treatments.
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This led scientists to investigate the role that the microbiome – trillions of bacteria, viruses, fungi and other single-celled organisms – plays in the development of bowel cancer.
Further down the line, the researchers said that looking for DNA damage fingerprints like the ones associated with colibactin in the cells of the gut lining could be used to identify those who are at a greater risk of developing the disease.
Professor Philip Quirke, Grand Challenge co-investigator at the University of Leeds, said: ‘Our goal is to understand the causes of bowel cancer, so discovering the role of colibactin represents an important step.
‘As a Grand Challenge team, we are now looking at other bacteria and their toxins associated with bowel cancer, and we hope to identify more DNA damage fingerprints to paint a better picture of risk factors.
‘We will then need to work out how we can reduce the presence of high-risk bacteria in the gut. But this is all in the future, so for now people should continue to eat a healthy diet and participate in bowel cancer screening.’
John Barnes, patient advocate for Grand Challenge said: ‘As a cancer survivor, I don’t want others to go through what I’ve gone through. Catching bowel cancer at an earlier stage while it’s still treatable has the potential to save thousands of people’s lives.
‘This brilliant research gives me hope that people may not have to suffer from bowel cancer in the future.’
Nicola Smith, senior health information manager at Cancer Research UK, said: ‘The more doctors understand about how bowel cancer develops, the better they will be at detecting it and helping people reduce their risk.
‘But there are already things that people can do right now to help reduce their risk of bowel cancer. Not smoking, keeping a healthy weight, eating a diet high in fibre and low in red and processed meat will all help. And for those who are eligible, participating in bowel screening can help to detect the disease at an early stage.’
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