Something in my Gut…

A dysbiosis paradox.

From my book Reservations for Nine: Chapter 3. “Misbehaving Cells: “…perhaps, cancer is a disease wherein a mutated gene sits dormant until it’s activated by something in its environment or an external catalyst barges in and sets the cancer cells in motion.” And further on…"The thought that Patrick {while in his late teens] perhaps had either a healthy tissue environment that was primed for tumor development or an inherent genomic instability—something that lay hidden until being coaxed to expose itself and do its malicious work by something else—was frightening.”

The book was written over a three-year period from 2020 to 2023. The final version of that particular chapter was realized during the fall of 2023.

Fast forward to the present.

April 24. A news release alert appeared in my Inbox. The Subject line read: “Check out this link via EurekAlert! and University of California - San Diego.”

A single, captivating sentence occupied the email body: “Childhood exposure to bacterial toxin may be triggering colorectal cancer epidemic among the young.”

My curiosity shot up like the mercury in a thermometer immersed in boiling water.

After making sure that it wasn’t a phishing attempt, I paused and clicked the link that was provided. It opened to a news release about a new study that was published the previous day in the prestigious journal Nature.

The first sentence of the body of the news release read: “An international team of researchers led by University of California San Diego has identified a potential microbial culprit behind the alarming rise in early-onset colorectal cancer: a bacterial toxin called colibactin.”

(Colibactin—an unstable genotoxin produced by certain strains of Escherichia coli, a gram-negative bacterium commonly found in our intestines and one that harbors the pks genomic island, linked to colorectal cancer. A colibactin mutagraph refers to the specific pattern of mutations left in DNA by its genotoxic activity.)

Could it be? Has the medical mystery of the rising incidence of early-onset cancer, one that’s tortured and since haunted me and my family, (and countless others) since September 2017, been…solved?

For the first time in what’s felt like a lifetime, hope suffused my heart, gently easing aside the shadows of grief that have long taken root within me.

Within hours, search engine results pages listed hundreds of web pages related to the keywords Nature and colibactin. I quickly scanned through the upper half of the first page, wanting to get to the article, only to find that it wasn’t yet available for viewing or downloading.

The purpose of the study, titled: “Geographic and age variations in mutational processes in colorectal cancer,” was broad and epidemiological: to analyze mutational patterns in colorectal cancer and understand geographical differences. More specifically, “…[to] investigate whether variation in mutational processes contributes to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. (1)”

The findings, however, turned out to be quite specific and surprising: a novel age-related microbial risk factor for colorectal cancer. The findings were described as being “…somewhat incidental…” by the lead study author.

More specifically stated, the research revealed a strong link between early-life exposure to colibactin-producing bacteria and the rising incidence of early-onset colorectal cancer (EOCRC). Studies analyzing 981 colorectal cancer genomes across 11 countries found that colibactin-induced DNA mutation patterns (SBS88 and ID18) were 3.3 times more prevalent in adults diagnosed before age 40 compared to those over 70. These mutations, which arise during the first decade of life, create a “molecular head start” by damaging DNA and accelerating tumor development—potentially explaining why younger adults are developing colorectal cancer decades earlier than previous generations.

A couple of days later, a PDF of the article was firmly nestled in my iPad. To say it was an interesting read would be a profound understatement. One sentence was notable: “…the mutation burden caused by this early life mutation burst can endow affected colorectal crypts with the equivalent of decades of mutation accumulation, and this head start could thus plausibly result in an increased risk of early-onset cancers (1).”

In infants, toddlers, and young children, several pathways to acquiring colibactin exist: the route of childbirth (vaginal delivery versus C-section), breastfeeding, direct transmission via intimate physical contact between mother and infant or being in close and crowded living quarters (daycare and pre-school centers, small apartments, etc.), and over-use of antibiotics. The over-use of antibiotics—referred to as “carpet-bombing” of the gut by a prominent physician author—has been linked to various health issues. Estimates suggest that about five to ten percent of children and adults in developed countries harbor pathogenic strains of Escherichia coli.

While detecting colibactin in adults is challenging, its unerasable mutatagraph snapshot remains, its potentially lethal fingerprint lying in wait until an activist triggers its rogue, malevolent behavior.

Over the ensuing days, many major national and local media news outlets broadcasted about the study, including articles in National Geographic and NPR. (One publication, the so-called SciTechDaily, referred to it as a DNA “Time Bomb”. A bit embellished perhaps, but an apt description.

I thought back to some of the research I did while writing my book. I knew that, in the search for causative agents of EOCRC, several non-genetic predisposition suspects were being investigated: various exogenous environmental or lifestyle carcinogenic exposures (smoking, alcohol, and pollution), diets heavy in ultra-processed foods, obesity, sedentary lifestyle, and the gut microbiome.

The microbiome, the body’s ecosystem of microorganisms, contains nearly 40 trillion microorganisms, of which 97 percent of them are in the gastrointestinal tract, especially the colon. They play an important role in maintaining good health, mediating a wide range of physiologic functions. At times their effects are protective and beneficial, conferred by organisms like Akkermansia, Lactobacillus, Ruminococcus bromii, and Bifidobacterium. Other times, they are pathogenic and carcinogenic, from Fusobacterium nucleatum and Helicobacter pylori. Symbionts and pathobionts. Guardians and threats. Sometimes promoting anti-inflammatory activity; other times producing and sustaining inflammation. Alterations of bacteria and fungi may promote carcinogenesis. Studies in JAMA, Nature and Gut compared both young-onset and later-onset colorectal cancer patients to young and healthy people in control groups. The findings suggested that the patients with cancer had fewer, and different species in their gut microbiome. Early-onset colorectal cancer patients had slightly different organisms than those found in the older-onset cohort (2) (3).

The irony of this dysbiosis paradox struck me. Even though it’s still just a casual generation of hypotheses worthy of ongoing investigation, I wondered if this genotoxin revelation was poised to solidify into undeniable fact. (Several of my key brain regions reminded me to be cautious about assuming causality versus correlation.) It felt a bit overwhelming.

Did my son, and so many other unfortunate young adults, die because of damaged and misbehaving gut bacteria that lead to carcinogenesis? (Oddly, I remembered what killed the Martian invaders in H.G. Wells’ The War of the Worlds—microorganisms.)

How strange that the very organisms meant to protect us could, when out of balance, become a threat.

Obviously, additional research is required. Can a definitive causal link between colibactin's residual effects and early-onset colorectal cancer be established? If confirmed, is it possible to create a test that accurately identifies a colibactin-induced oncogene? Furthermore, how can we ascertain its functional status? Who would be the appropriate candidates for such testing? What actions should be taken based on the results, and what are the feasible options? Is a RCT necessary to evaluate the balance between benefits and harms and to compare effectiveness of treatment? (I’ll skip the how big will the study cohort and the duration need to be to have enough statistical power questions for now.) Given the pressing nature of early-onset colorectal cancer, how much longer can we delay awaiting results? How many more individuals may develop, suffer, or die from this disease while the medical and scientific communities adhere to orthodox approaches in pursuit of conclusive evidence?

Imagine if it turns out that the scourge of early-onset colorectal cancer can for the most part be stopped in its tracks by teens and young adults taking probiotics, eating a Mediterranean-style diet, not smoking, limiting alcohol consumption, and staying active.

But if it can’t be stopped, perhaps it can be detected earlier when doing something can halt it.

Perhaps a part of the how question has been answered. Only time will tell.

The why question will remain a spiritual one.

1. Díaz-Gay, M., et al. "Geographic and age variations in mutational processes in colorectal cancer." Nature (2025). Published April 23, 2025

2. Harris E. Bacterial Subspecies Linked with Aggressive Colorectal Cancer Tumors. JAMA. 2024 May 14;331(18):1526.

3. Kong C, Liang L, Liu G, Du L, Yang Y, Liu J, Shi D, Li X, Ma Y. Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer. Gut. 2023 Jun;72(6):1129-1142. doi: 10.1136/gutjnl-2022-327156. Epub 2022 Aug 11. PMID: 35953094.