Scientists have finally learned how a common gut bacteria fuels colon cancer, paving the way for preventative treatments that can protect the organ from early damage. In 2009, a landmark study found that Bacteroides fragilis drives tumour formation by secreting a toxin that damages the lining of the colon, potentially leading to cancer. But until now, the exact mechanism the toxin uses to attack cells remained a mystery.
Breakthrough Discovery
Now a team of US researchers have uncovered the missing link, paving the way for better detection and treatment of a disease surging in under 50s. The toxic bacteria must first bind to a host receptor, dubbed claudin-4, before it can cause damage.
'We've made several attempts over time to identify the receptor, so this is an exciting moment,' Professor Cynthia Sears, study lead author from Johns Hopkins University School of Medicine, said. 'Understanding how bacterial toxins work can open doors to new approaches for detection and therapy for associated diseases, including diarrhea, colorectal cancer and bloodstream infections.'
The discovery has already led to an intervention that successfully blocked the toxin's effects in animal models. Now the race is on to do the same in humans.
How the Toxin Works
Toxic bacteria triggers chronic inflammation in the gut by attacking protein cells that protect the colon's delicate barrier. The common gut bacteria is present in around 20 per cent of healthy individuals and has a powerful ability to trigger colon inflammation and tumour growth.
Colorectal cancer claims over 17,000 lives each year in the UK alone. Rates in under 50s continue to climb, increasing by 75 per cent in under-24s since the 1990s. But scientists are yet to identify a single smoking gun with poor diets, increasing obesity levels and exposure to microplastics thought to be major contributors.
Colorectal cancer is typically diagnosed at a late stage, when treatment is difficult, because it causes few symptoms early on which are often mistaken for less serious problems like IBS.
Study Details
The scientists hope their finding will pave the way for earlier detection and one day inform treatment for bacteria-associated diseases including colon cancer. The study, published in the journal Nature, tested thousands of genes to find out which ones affect cancer growth.
Previous research found the bacteria triggers chronic inflammation in the gut by attacking protein cells essential for maintaining the colon's protective barrier. But the bacteria didn't seem to be attaching itself to the protein directly. Some other elusive mechanism was at play.
After ruling out thousands of potential genes involved, the researchers pinpointed claudin-4 as the culprit. When they knocked out claudin-4 receptor cells, the bacteria had nothing to cling to, leaving the colon's protective barrier untouched.
'It took a while to validate the approach, but once we were able to the screen, claudin-4 was a clear, resounding top hit,' the researchers said. 'That was an exciting moment.'
To confirm that the toxin and the receptor cells were physically locking together, the team looked at how the two organisms interacted in a test tube, providing the first physical evidence of the binding interaction. They then made a dummy claudin-4 protein to see if they could prevent the toxin from binding to colon cells in mice.
Results in Animal Models
Results showed that, in mice treated with the dummy proteins, the bacteria bound to the decoys instead of claudin-4 receptor cells, protecting the mice from toxin induced damage. The team is now exploring how to block the toxin in humans.
It comes as a team of British researchers declared last month that obesity is a key factor for the rising rates of cancer among younger people in England. There are 11 types of cancer, including bowel cancer, that are increasing among under 50s. And obesity is the only known behavioural risk factor that has been increasing in younger adults over the last two decades while smoking, alcohol and physical inactivity have all remained stable or in decline.
Maintaining a healthy weight has been shown to prevent around 20 per cent of bowel cancers. But an imbalance in gut bacteria could also be behind the mysterious rise, experts say, with today's youngsters having been exposed to more antibiotics than previous generations, making the gut microbiome more vulnerable to toxic invaders. Diets high in ultra-processed foods may also play a role in the development of bowel cancer, fueling the growth of pro-inflammatory gut bacteria, which is thought to increase the risk of early onset cancer.
