Gut microbiome associated with precancerous lesions, future onset of colorectal cancer
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Key takeaways:
- Whole microbiome composition was linked with preexisting lesions and the future development of adenomas.
- Microbiome diversity decreased in individuals who developed colonic lesions after fecal sampling.
The gut microbiome is linked to preexisting colorectal lesions, as well as future development of lesions, according to a presenter at UEG Week, and including microbiome biomarkers may improve noninvasive tests for colorectal cancer.
“We know the gut microbiome has been linked to colorectal cancer both directly by inducing renal toxicity or long-standing inflammation, but also indirectly through many different mechanisms,” Ranko Gacesa, MSc, PhD, a postdoctoral researcher at University Medical Center Groningen in the Netherlands, said during his presentation.
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“One of the questions which we are trying to answer in this study is what comes first? Does colorectal cancer change the gut microbiome, or does the gut microbiome actually cause cancer or at least come before the cancer? It’s important both for diagnostics and for fundamentals of science ... ideally, we don’t want to detect cancer when it is already there because it is difficult to treat. We want to detect it as early in development as possible.”
Using the Dutch Microbiome Project and Dutch nationwide pathology database, Gacesa and colleagues identified 8,208 individuals who underwent colonic biopsies over the last 5 decades. They assessed gut microbiome function and composition in individuals who developed precancerous colorectal lesions before fecal sampling between 2000 and 2015 (n = 219) and after fecal sampling between 2015 and 2022 (n = 315), and compared them with 2,123 matched controls.
Additionally, researchers investigated specific bacterial strains and their functions by reconstructing their genomes from metagenomic data.
Gacesa noted there were 26 CRC cases, 24 advanced adenomas, 131 adenomas and 68 serrated polyps among participants with precancerous lesions before sampling, and 29 CRC cases, 73 advanced adenomas, 128 adenomas and 51 serrated polyps in those who developed lesions after sampling.
Results showed a decrease in microbiome diversity in individuals who developed colonic lesions following fecal sampling.
“Adenomas, both preexisting and ones developed in the future after [fecal] sampling, are significantly linked to whole microbiome composition,” Gacesa said.
Moreover, microbiome composition and function were different in those with preexisting or future lesions, researchers reported, and also varied by lesions, including CRC, high- or low-grade dysplasia or serrated polyps.
Of note, bacterial species from the family of Lachnospiraceae and the genera Roseburia and Eubacterium were associated with future development of lesions.
Gacesa told Healio these findings still need to be validated in other populations and clinical trials before implementation into patient care. “Assuming further studies are successful, it could in the future improve prevention of colorectal cancer by contributing to new and better noninvasive tests for this disease.”
Gacesa added: “Our next step is to look at bacterial metabolites linked to colorectal pathologies and bacteria detected in this study. This is important both to understand the biology behind our findings and because it is easier and more practical to develop tests for metabolites and chemicals, as opposed to tests targeting bacteria.”
Perspective
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Gail A.M. Cresci, PhD, RD, LD
These data support prior studies showing that disruption in the gut microbiome accompanies colorectal tumorigenesis, and that these changes may be causative. There is crosstalk between the host and gut microbiome; therefore, disruption in gut microbiome composition and function could dismantle this communication and compromise host cell integrity. There are many genetic and environmental factors, among others, that can affect the gut microbiome.
A research area of interest in our group is how environmental factors may affect changes in gut microbiome composition and function and lead to cancerous lesions. In a healthy state, the gut microbiome produces many beneficial metabolites for the host. Increasing our knowledge into how a disruption in gut microbiome and its generation of metabolites differs longitudinally in individuals with and without precancerous or cancerous lesions could shed light into new potential biomarkers for early detection of cancer development and preemptive intervention.
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Gacesa R, et al. Development of precancerous colonic lesions is associated with gut microbiota in the Dutch microbiome project cohort study. Presented at: UEG Week; Oct. 14-17, 2023; Copenhagen, Denmark (hybrid meeting).
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