Colorectal Cancer and Childhood Exposure to a Common Gut Bacteria

Colorectal cancer (CRC) rates are rising in adults under 50, with incidence patterns varying significantly by global region.¹ As researchers dig into the age- and geography-related shifts, they’re zeroing in on risk factors behind early-onset cases. Environmental exposures and certain lifestyle factors can leave their mark on a person’s health and imprint characteristic patterns of somatic mutations in the genome, known as mutational signatures.²

Unraveling the Link Between Colorectal Cancer and Gut Bacteria

Ludmil Alexandrov, a cancer geneticist at the University of California, San Diego, combines traditional and mutational epidemiology to analyze genomes for genetic patterns that may be responsible for the varying CRC incidence rates. Alexandrov and his team found that early-life exposure to colibactin, a DNA-damaging toxin produced by certain strains of Escherichia coli in the gut, is strongly linked to early-onset CRC.³

The team used whole-genome sequencing and cataloged mutational patterns from more than 900 patients with CRC across 11 countries and four continents with intermediate to high incidence of CRC. Among these, mutations linked to colibactin exposure stood out.

Colibactin: A Bacterial Toxin's Role in DNA Damage

In humans, E.coli is part of a healthy gut microbiome; however, certain strains of E. coli can produce colibactin, a mutagenic compound linked to double-stranded DNA breaks and a possible driver of CRC.⁴ It results in two traceable mutation types: single base substitutions (SBS) and indels (ID).

Childhood Exposure to Gut Bacteria: A Precursor to Early-Onset CRC?

Previous research, including that from Alexandrov’s group, had found colibactin-related mutations in 10 to 15 percent of all CRC cases.⁵ However, in this study, the researchers noted more frequent mutations in early-onset cases: Mutations SBS88 and ID18 were 3.3 times more common in individuals diagnosed before age 40 than those over 70.

“These mutation patterns are a kind of historical record in the genome, and they point to early-life exposure to colibactin as a driving force behind early-onset disease,” said Alexandrov in a press release.

Because prior studies found that such mutations arise within the first decade of life, the team wanted to see if their samples exhibited a similar pattern.⁶ To determine when these mutations occurred, the researchers classified mutations in all tumor cells as early clonal and those that appeared in only some cells as late clonal. They found that SBS88 and ID18 were enriched in early clonal mutations, suggesting that colibactin-related mutations occur early in tumor development. In addition, the researchers also found that colibactin-related mutations were linked to additional driver mutations known to promote cancer progression.

Implications for Colorectal Cancer Prevention and Treatment

“If someone acquires one of these driver mutations by the time they’re 10 years old,” Alexandrov explained, “they could be decades ahead of schedule for developing colorectal cancer, getting it at age 40 instead of 60.”

“This reshapes how we think about cancer,” said Alexandrov. “It’s not just about what happens in adulthood. It’s about what happens in the first decade of life—maybe even the first few years. Sustained investment in this type of research will be critical in the global effort to prevent and treat cancer before it’s too late.”

Frequently Asked Questions (FAQs)

Q1: What is early-onset colorectal cancer? Early-onset colorectal cancer (CRC) refers to cases of colorectal cancer diagnosed in individuals under the age of 50. Incidence rates for this demographic have been increasing globally.

Q2: How is childhood exposure to gut bacteria linked to colorectal cancer? New research suggests that early-life exposure to certain strains of Escherichia coli (a common gut bacteria) that produce a DNA-damaging toxin called colibactin may leave mutational signatures in the genome, contributing to the development of early-onset colorectal cancer decades later.

Q3: What is colibactin and how does it affect DNA? Colibactin is a mutagenic compound produced by specific strains of E. coli found in the gut. It is known to cause double-stranded DNA breaks and results in traceable mutation types, specifically single base substitutions (SBS) and indels (ID), which can drive cancer progression.

Q4: What are the implications of this research for colorectal cancer prevention? This study highlights the importance of early-life environmental exposures in cancer development. Understanding how childhood exposure to common gut bacteria can lead to colorectal cancer may open new avenues for prevention strategies, potentially by targeting specific bacterial strains or mitigating their effects early in life.