Researchers have identified significant variations in the gut microbiome of patients with precancerous colorectal lesions, suggesting a potential correlation between gut bacteria and the onset of precancerous lesions and colorectal cancer, according to new findings presented by Gacesa et al at United European Gastroenterology (UEG) Week 2023. The results of the study indicated potential new avenues for enhancing the detection and prevention of colorectal cancer.
Background
Colorectal cancer—the second most common cancer type and second leading cause of cancer-related mortality in Europe—typically develops from precancerous lesions within the gut, making the removal of these lesions an effective strategy for preventing colorectal cancer. However, existing noninvasive detection methods such as the fecal immunochemical test may produce a high number of false-positives, leading to unnecessary colonoscopies.
“The connection between the gut microbiome and precancerous lesions has been underexplored, leaving uncertainty about whether gut bacteria can predict the future onset of colorectal cancer,” explained lead study author Ranko Gacesa, MSc, PhD, of the University Medical Center Groningen.
Study Methods and Results
In the recent large-scale prospective study, the researchers used data from the Dutch Microbiome Project and the Dutch nationwide pathology database to identify 8,208 patients who underwent colonic biopsies in the past 50 years. The researchers then analyzed the function and composition of the gut microbiomes of 214 patients who developed precancerous colorectal lesions prior to fecal sampling between 2000 and 2015, as well as 305 patients who developed precancerous lesions following fecal sampling between 2015 and 2022. Both groups were compared with 202 patients who had normal colonoscopy findings and individuals in the general population. To gain a deeper insights into the gut microbiome’s role, the researchers also examined specific bacterial strains and their functions within the gut by reconstructing their genomes from metagenomic data.
The researchers found that the patients who developed precancerous lesions following the fecal sampling exhibited increased diversity in their gut microbiome compared with those who did not develop the lesions. Further, the composition and function of the gut microbiomes differed among patients with preexisting or future lesions and varied based on the type of lesions. Of note, bacterial species from the family of Lachnospiraceae as well as the genera Roseburia and Eubacterium were linked with the future development of precancerous lesions.
Conclusions
“While we didn’t investigate mechanisms in this study, it is known from previous research that some of the bacterial species identified may have properties that could contribute to the development of colorectal lesions. A bacterium called Bacteroides fragilis, for example, is known to produce a toxin that can lead to chronic low-grade inflammation in the gut. Prolonged inflammation is believed to be potentially genotoxic and carcinogenic, meaning it may cause genetic damage and promote cancer,” emphasized Dr. Gacesa. “Our findings suggest that the microbiome could act as a valuable tool to improve existing tests, advancing early detection methods for precancerous lesions and colorectal cancer,” he concluded.
