Transcription
There’s something kinda worrying going on in the world of cancers. I mean, it’s cancer, all worrying. More and more people under the age of 50 are being diagnosed with colorectal cancer. In some countries, the number of cases has even doubled in recent decades. Which is strange, since typically colorectal cancer is a disease that affects older adults. And what’s even stranger is that these young people don’t seem to have any of the usual risk factors for colorectal cancer, like an inherited genetic mutation. Plus, even once they realize, the damage may have already been done. But after some sleuthing, scientists might have an answer… in the form of a common gut bacterium.
[INTRO] While not every country has seen uniform increases in early-onset colorectal cancer, at least 27 of them have seen a jump. In fact, in many higher-income nations, the overall incidence of colorectal cancer has gone down. Which makes the rise in young people all the more dramatic. And if the number of youth cases keeps going up, then researchers think colorectal cancer could become the leading cause of cancer-related death among young adults by 2030! That’s soon.
Researchers have been scrambling to find a cause in order to prevent those deaths, and they’ve largely come up empty. But thanks to a 2025 study published in the journal Nature, they may have found an answer. The authors sequenced the entire genome of almost 1,000 cancer samples from both early and late-onset cases, from 11 countries, across four continents. Which is pretty comprehensive as these things go. What they saw was a specific pattern of DNA mutations that looks like the pattern left behind by a bacterial toxin called colibactin. And these mutations were 3.3 times more common in early-onset cases – which here meant adults under 40 – than in those diagnosed after the age of 70.
Now, researchers already knew that colibactin is linked with certain cases of colorectal cancer, but this is the first time they’d shown a link between it and early cases. And they think that those DNA mutations are building up early in life. Like, we’re talking childhood early. Which basically puts them decades ahead of schedule for developing colorectal cancer.
So, what is colibactin and how does it lead to cancer? Colibactin is what’s called a genotoxin, a toxin that damages DNA. It’s made by certain strains of E. coli bacteria. And while you might hear about E. coli in scary contexts like food poisoning or UTIs, it’s often found as a – usually – harmless resident of your gut. E. coli make colibactin in order to fight off other bacteria. Problem is, it doesn’t just damage bacterial DNA, it’s pretty harmful to human DNA too.
Until as recently as 2020, we didn’t really know a ton about how colibactin damages our genetic material. That’s because this sneaky toxin is tricky to study: it doesn’t last very long in a lab setting, and it’s near impossible to separate out from other substances that E. coli makes – some of which are actually helpful for our bodies! It wasn’t until other scientists created mini petri-dish organ models called organoids, and improved mathematical techniques for analyzing mutations, that researchers could figure out what colibactin was up to.
In a 2020 study, biologists infected these mini-organs with colibactin-making E. coli and looked at how the DNA in those cells changed. What they discovered was a mutational signature – a kind of calling card colibactin leaves behind when it reacts with DNA. The same calling card was detected by the researchers in the 2025 study. They can tell because it has two key mutations. One, called SBS88, frequently swaps out one of the four building blocks of DNA, a thymine, for a different one, usually cytosine. Another mutation, called ID18, inserts or deletes a small section of DNA. This leads to what’s called a frameshift. Basically this means the DNA isn’t read in the way that it should be. Imagine you have the sentence “the fat cat sat.” Now, get rid of the “e” but keep the spacing the same. You get “thf atc ats at”... it doesn’t make sense anymore. In the same way, if the spacing of the genetic code gets messed up, the cell’s machinery can’t read it correctly. The reading frame is shifted.
These two mutations are driver mutations, meaning they drive or spur on the development of cancer. Specifically, what might be happening with colorectal cancer is that colibactin – with all its snipping and swapping of DNA – might be turning off a copy of a gene called APC. APC is a tumor suppressor gene, meaning one that’s really important for keeping cancer in check. And it’s especially important when it comes to colorectal cancer.
Ok. But what does this have to do with early cases specifically? It’s not clear. The authors of the 2025 study propose that colibactin-producing strains of E. coli might have been getting more common in the second half of the 20th century, leading to more of the toxin in our guts. What’s really important here – and scary – is that these mutations tend to occur early in life. Frighteningly, one of the researchers suggested that could represent a head start for the cancer of up to 20 years, developing at age 40 instead of age 60. So it’s not like you can start taking probiotics in your 30s to ward off the bacteria, since the damage has already been done. Which I don’t like! As a 45 year old.
And there’s still a lot we don’t know. Like, how are children being exposed to these bacteria? Is it something we can prevent? And are you more likely to be exposed if you have a certain lifestyle or live in a particular place? Researchers are now starting studies to try and answer those questions. And they’re developing early detection tests that hunt out colibactin-related mutations in stool samples to catch potential cancers before they get too far.
But until we have more answers, there are things you can do too. If you’re 45 or older, you can get screened, or earlier if you have any worrying symptoms. Screening means a colonoscopy, I’ve had like ten of them. It’s not a big deal, you can do it.
In addition, it’s more important than ever for younger folks to be on the lookout for potential early signs of colorectal cancer. So here is what those are: Changes in bowel habits that last more than a few days, rectal bleeding or blood in your stool, urgency to go that’s not relieved by going, abdominal pain, weakness and fatigue, or unintended weight loss. Now all of that stuff could be explained by other things as well. But it’s good to know so that if you’re experiencing that stuff, you can go see a doctor, especially more than one of those things. If it’s nothing, you will find out that it is nothing and you will feel better! There’s no better moment for me than after a colonoscopy when they’re like, “You don’t have colon cancer.”
It’s good news that researchers are making progress on this mystery even though there’s a lot more work to be done. Understanding the cause is always the first step. Unfortunately, it’ll take time to put this understanding into action, so in the meantime, be informed, see your doctor if anything’s weird, and keep rooting for those scientists.
[OUTRO]