Sunday Science by Go-UnPro Episode 1: 2025_11_02

In this first episode of Sunday Science, we explore a few articles showing the carcinogenic potential of a strain of E coli (pks+ or colibactin-producing) that produces a DNA mutational toxin.  Evidence from the discussed articles shows that this bacteria could be responsible for a high percentage of early onset (under age 50) colorectal cancer (CRC).  CRC at this age is increasing and now encompasses 10% of all CRC, which percentage is growing by 2% per year.  Up to 68% of these cancers have evidence of the hallmark mutations and presence of the pks+ E coli above.  Diets high in fiber decrease and diets low in fiber increase the presence of this bacteria.  As we elucidate the particular mutations associated with this and other carcinogens, we can detect these mutations within the DNA of each cancer patient.  The data shows evidence of this bacteria being present in those with CRC under age 50, and it is more prevalent in countries that have a higher incidence of CRC under age 50, and likely has been present since an early age, such as the first 10 years of life.

A simple arithmetic problem of subracting 40 years from 2015 when these early-onset CRC began their increase, yields the year 1975 which is when we began to incorporate processed foods and refined sugar and high-fructose corn syrup into our diet.  This and the data of onset at age 10 and before, begs us to consider what we are doing to our children and the possibility that there are a whole 40 years of children that are increasing their processed food intake.  How many early-onset CRC patients will there be 40 years from now?  MIcrobiome and genetic mutational research into other cancers such as oropharyngeal, bladder, and anal carcinoma could soon provide these answers.  

References

• Insights into the role of the intestinal microbiota in colon cancer. Sofia Oke and Alberto Martin.  Ther Adv Gastroenterol 2017, Vol. 10(5) 417 –428

  • Microbiome and colorectal cancer: Unraveling host-microbiota interactions in colitis-associated colorectal cancer development.  lMingsong Kang, Alberto Martin. Seminars in Immunology.  Volume 32, August 2017, Pages 3-13

  • Gut Microbial Metabolism Drives Transformation of Msh2-Deficient Colon Epithelial Cells. Antoaneta Belcheva1 . Cell.   Volume 158, Issue 2p288-299July 17, 2014

  • Oliero M, Hajjar R, Cuisiniere T, Fragoso G, Calvé A and Santos MM (2023) Inulin impacts tumorigenesis promotion by colibactinproducing Escherichia coli in ApcMin/+ mice. Front. Microbiol. 14:1067505.

  • Dietary fibre counters the oncogenic potential of colibactin-producing Escherichia coli in colorectal cancer. Alberto Martin.  Nature Microbiology  10: 855-870.

Sunday Science 2025_11_02.m4a

Comprehensive Summary of Key Topics, Insights, and Conclusions

Key Topics

Colon cancer incidence and mortality

Rising incidence of early-onset colon cancer in young people

Potential links between diet, microbiome, genetics, and colon cancer development

Screening and diagnosis of colon cancer

Role of colibactin-producing E. coli and its association with colon cancer mutations

Dietary factors and their impact on the microbiome and colon cancer risk

Insights and Takeaways

Colon cancer is the second leading cause of cancer deaths globally, but the fourth most common diagnosed cancer, indicating it may be more deadly than other cancer types.

The incidence of early-onset colon cancer (under age 50) has been rising, with a 51% increase since 1994, and now accounts for 10% of all colon cancer cases.

Factors like diet, microbiome, and genetics play a significant role in the development of colon cancer, especially in young individuals.

Colibactin-producing E. coli strains are associated with specific mutation patterns in colon cancer, and their prevalence is higher in younger cancer patients.

Dietary factors, such as low-fiber, high-fat, and high-sugar diets, can promote the growth of colibactin-producing bacteria and increase the risk of colon cancer.

Fiber-rich, plant-based diets and a healthy microbiome may be protective against colon cancer development.

Conclusions and Decisions

Early-onset colon cancer is a growing concern, and the potential link between childhood diet, microbiome, and colon cancer development later in life needs further investigation.

Screening guidelines for colon cancer may need to be revised to include younger individuals, especially those with risk factors.

Promoting a healthy, fiber-rich, and plant-based diet from an early age may be crucial in preventing the development of colon cancer.

Further research is needed to understand the complex interplay between diet, microbiome, genetics, and colon cancer, as well as the potential role of probiotics and other interventions in modulating the microbiome and reducing cancer risk.

Educating the public, especially parents, about the importance of a healthy diet and its long-term impact on colon cancer risk in their children is essential.

[ 00:00:00 ]Welcome to Sunday Science, where we dive into a few recent scientific articles and their translation into our modern lives. Here is your host, Brent W. Lartz, MD. All right! Today we are having our first episode of Sunday Science from Go On Pro. This is dated November 2nd, 2025. We're going to discuss how your diet, your microbiome, and genetics can cause colon cancer in young people. Not only that, but it could have been your diet and your microbiome in childhood that could have started all the whole process here. Colon cancer causes approximately 1. 9 million cases per year and 900, 000 deaths. It is the second leading cause of cancer deaths. globally while being the fourth most common diagnosed cancer. What does that mean?

[ 00:00:49 ]If it's the second leading cause of cancer deaths but the fourth most common diagnosed cancer, it means it could be somewhat more deadly than a couple of other types of cancer. In the U. S., 154, 000 new cases occurred in 2023, and the incidence is declining, and there are 52, 900 deaths in the year 2023. Deaths also declining, likely related to increased screening and increased lifestyles better lifestyles. Five-year survival of localized colon cancer is 91 and for all stages, it is 65%. Factors including a sedentary lifestyle, diet high in processed. foods and red meat, smoking, lack of exercise, ethanol, genetics, inflammatory bowel disease, and certainly the outcomes of these cancers are associated with access to care.

[ 00:01:56 ]Early colon cancer statistics: the incidence is rising in those under age 50, and 55 years of 10% of colon cancer is in patients who are under age 50, rising approximately 2% per year, and that's a 51% increase since 1994. Approximately 7, 000 to now more than 15, 000 cases per year in those under age 50. Potentially another statistic that is bantered about is 20% of those under age 55; colon cancer is rising as well. It used to be that this was only seen in young persons. If they had a genetic familial basis for colon cancer, these are persons with a couple of different genetic illnesses, one called familial adenomatous polyposis. That syndrome is autosomal dominant in about 50% of the cases, and most of the rest are new mutations that we can now determine.

[ 00:03:12 ]These persons have colons that are filled with polyps, and hence, if you have a colon filled with polyps by the time you're age 30 or 40, all the more likelihood you're going to get colon cancer; and hence, some of these persons have their colons taken out prophylactically prevent colon cancer. However, now most of these, or at least some of these. cases of early colon cancer are potentially linked to the microbiome. Early colon cancer is now the deadliest cancer in young men, and it is the second most deadly cancer in young women. Often, this is related to a delay in diagnosis because, at age 40, before we were less likely to have a uh tests to diagnose and/ or screen for these illnesses, because it was very uncommon.

[ 00:04:20 ]But given the increased prevalence and insulin incidence of these diseases, we are now seeing the screening ages dropping uh, to what they used to be. Um, 54% of patients with early cancer were misdiagnosed as hemorrhoids, uh, irritable bowel syndrome, et cetera. 36 saw three or more doctors before their diagnosis, and the symptoms of which change in bowel habits, bleeding, abdominal pain. Um, now we have screened and a recommendation to screen at age 45 or sooner if you have risk factors. Um, there are genetic and environmental causes. The type and the pattern and the location of the mutations causing these colon cancers depend on the chemical and potentially tobacco and other carcinogens have a certain pattern of mutations that are associated with them.

[ 00:05:28 ]And these are being discovered and have been discovered for many years, but now we're finding a particular type of mutation. Um, that is associated with your bacteria in your intestine. Let's talk a little bit about the mutations in colon cancer. The first we're going to talk about is adenomatous polyposis coli tumor suppressive gene. When you get a mutation in this gene, you will acquire a benign adenoma. This mutation in this gene is present present in over 80% of colorectal cancer. Its function is to maintain homeostasis of the gut epithelium. So you can see why this particular mutation would potentially cause inflammation and then cause polyps and then cause an adenoma. Epidermal growth factor receptor mutations then potentially. can add on to that mutation for colorectal cancer progression.

[ 00:06:42 ]And then subsequent mutations, there are multiple ones: KRAS, PTEN, and TP53 are a few of the other mutations. Screening for colon cancer, the gold standard is colonoscopy, but there are also a couple of other tests. You've all heard of these tests that are, um, found on commercials during multiple different, uh, broadcasts on, uh, cable TV. Uh, or there's also a blood DNA test. The difference is the colonoscopy is the gold standard, and this is the only way that you can remove some of these, uh, pre-cancerous polyps before they develop cancer. Uh, the stool for DNA tests are good. tests at screening for precancerous but they do miss some of these. And they're also their specificity is not, you could have false positives. Um now there is a microbiome length.

[ 00:07:49 ]And here's where we're going to talk about this. There is, uh, there are colibactin-producing E. coli that are not the same strains that cause diarrhea. And you think about your hamburger or other types of food based caused by E. coli. These are different strains. Colibactin is a DNA mutagen and it is causes certain mutation patterns. And those mutation patterns can be detected in colon cancer. And hence we're going to be talking about that later, uh, in Some of these new articles we're going to be talking about three new articles, um, that are related to this. It is possibly related to exposure as a child because it takes a long time for these mutations to build up and also for them to now then acquire other mutations, um, requiring, uh, that are required to develop colorectal cancer.

[ 00:08:48 ]Up to 68% of colorectal colonized colorectal cancers are colonized with PKS E. coli. This is the colibactin-producing E. coli, also called PKS-positive E. coli. All right, we're going to be talking about first, um, an article in the Lancet Microbiome which was published in April of 2025. This, um, article had examined the genomes of 981 bowel cancer patients, their cancer cells in 11 countries. Under 40 cancer diagnosis, if you were diagnosed at age 40 or less, you were 3. 3 times more likely have colobactin mutations. If you were greater than 70 and you had colon cancer, it is more prevalent, this colobactin mutations countries that had higher rates of early onset cancer. These polyketide synthase positive E. coli strains produced E. coli, produced colobactin and hence then developed the colon cancer potentially. Another article from Nature Microbiology from 2025 studied dietary fiber and its inhibition of colobactin. They studied mice with three different types of either a low carb, low fiber diet, high fat, high sugar diet, or normal chow. The PKS positive bacteria induced senescence associated secretory phenotype, which further potentiated by inflammatory triggers, and mismatch repair deficient model

[ 00:11:06 ]was associated with increases in those PKS positive bacteria. The low carb, low fiber diet was associated with a higher amount of PKS positive bacteria. The high fat, high sugar diet and the normal chow were associated with low amount of PKS positive bacteria comparatively. One issue here is, what if you had a low carb, high fiber diet instead? of a high-fat, high-sugar diet or some other types of diets. Certainly, there are more than one type of different diet that you could study in this situation. Frontiers in Microbiology article from 2025 also showed that inulin, which potentially we think of inulin as being a good thing in our diet because it is a fiber that decreases inflammation in most patients. However, this article investigated inulin, um, because it was found potentially to be protective, but it also has tumor-promoting effects.

[ 00:12:29 ]This article showed that there was a if you had a combination of pks-positive bacteria instilled into these mice that were prone. to develop cancer. They were APC mutated mice. Then they were treated with DSS to stimulate tumors. If those pks positive mice were also then given inulin, then it promoted tumors in those mice. If a strain of E. coli deficient in colibactin, same pks positive mice, but they did not produce colibactin. If that was introduced, instead of the tumors were found. If you gave a paraprobiotic, which was pasteurized E. coli, same strain defect, actually a Nissl strain, which was a pasteurized paraprobiotic that also inhibited the tumor agenesis. Very confounding results here, suggesting that it's not just the pks positive but potentially. Maybe the um competition in the intestines of these mice with either other strains of E.

[ 00:13:57 ]coli or a paraprobiotic that has good factors produced by certain probiotic strains that was tumor-protective. Other colon cancer issues, you certainly need a driver mutation. And so that driver mutation may be these colibactin-induced mutations that were induced as a child. And then you need pro-cancer passenger pro-progression bacteria. So there are certain bacteria that induce the either directly producing compounds that cause DNA damage or inflammation that causes that damage. And then, once there is a mutation causing a tumor. Now you might need passenger progression bacteria. And this is another theory that your microbiome is important. Fecal transplants from colon cancer mice can transfer the disease to germ-free mice. This was discovered in 2013, quite a while ago, suggesting that there is something about the something in the feces in general, the bacteria that then produce back colon cancer in these mice.

[ 00:15:32 ]Then there is also evidence that microbial dysbiosis can affect some tumorigenesis as well. There are short-chain fatty acids that bacteria produce that could stimulate polyps. And then there is in persons such as those with Lynch. Syndrome, which is a syndrome that is prone to develop colon cancer. The microbes, if they are present in those patients, can produce 8-oxoguanine. Those 8-oxoguanine lesions produce a mismatch repair system dysfunction and, hence, your production of colon cancer in those patients. And, as we talked about, dysbiosis causes inflammation, and that can lead to colorectal cancer. And what do we all need to do about this? And this is certainly not that controversial because transformation requires acquisition of mutations. Those mutations are in suppressors and oncogenes, and it begins in the intestinal stem cells and can develop.

[ 00:16:49 ]over the course of your life. Studies have shown that high-fiber diets low in processed foods and low in red meats, and exercise, and maintaining a healthy weight is protective from developing colon cancer. Carcinogenic microbes colonizing a large portion of humans can potentially alter their host genetics but also contribute to the carcinogenesis in a host that already is predisposed by their genetics or their dietary composition or inflammatory dysregulation. Now we have to think about what about as parents? Do we really need to think about our children if we are feeding them now processed foods and red meats? is this the reason why we're now seeing the rapid increase in younger patients developing colon cancer? Because think about it: from around the year of 2015, when we first started to see this increase, what is important about that date?

[ 00:18:14 ]What is approximately 40 years before that date? 40 years before 2015 is 1975. 1975 is when we started really ramping up the processed foods, the increased sugars in our diet, high fructose corn syrups, and multiple of other different dietary changes from the from the revolution of processed foods that occurred in this country in 1975. Now go to 1985 and the different changes we had. then That is approximately 40 years ago. Now what's it going to be like when we get to be 40 years from now and 40 years from maybe 10 years ago? Certainly, over the last 10 years we have had an improvement in recognition that high fiber diets are important, and the prevalence of persons who are eating more vegan food, more whole food diets is increasing slowly.

[ 00:19:26 ]But what's going to happen 40 years from now? Is that percent of individuals with colon cancer, is it going to be even higher than now? Is it going to be instead of an incidence of of 10 of colon cancers, is it going to be 50 of colon cancer? We're going to have a wave in 10, 20 years where Instead of having 15, 000 cases per year, are we going to have 50,000, or are we going to be having 100, 000 cases per year and many more deaths until we start screening at age 40 or 35? Maybe even to take care of these polyps that were induced by the colibactin-producing E. coli. So something to think about, and that microbiome link, and what to do about our microbiome: probiotics, fiber, natural foods, whole foods, mostly plant-based diets.

[ 00:20:48 ]Going to be more and more studies that are going to elucidate the effects of these improved dietary changes to see if they make an impact on these colon cancer incidences. Or here's a question: Is it going to take many more years after that to discover that we need to have these whole food diets in the years from age zero and maybe in utero to from age zero to 10 years of age 20 years of age when we're not thinking about our diet when we're feeding our kids a lot of red meat and a lot of proteins because we need to induce their growth. We think they want to be weightlifters, football players, baseball players. So we pile on and take them out for steak and take them out for low fiber diet restaurants and fast foods and all of that.

[ 00:21:56 ]Is it going to really take until we realize that it's our children that we need to protect and not at age 40 and age 50 like myself when I'm starting to have a better diet now because I am learning about these things. Is it going to take until then before we figure out that it is our children that we need to be really impacting in the future? Thank you very much for this. I will include the references. There are approximately five different references here that I'll include in the show notes for this. Certainly, Alberto Martin is one of the important authors of these articles, but there are multiple other people, including Dr. Santos and others who are involved in this. There is an organization in the UK and worldwide that is looking into these different factors as well. And I'll include that in the show notes as well. Thank you very much for attending, and thank you, and have a nice rest of your Sunday. This is Sunday Science from Go Unpro.

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