Image of gut and intestines showing colorectal cancer highlighted in red.
Credit: Raycat/Getty Images

Quantitative methods paired with strict confounder control uncover more accurate microbiome colorectal cancer biomarkers, according to new research. Multiple microbial taxa have been put forward as potential cancer-associated biomarkers in the past, but this new study uncovers obscured contributions that may have resulted in incorrect associations. 

This study shows that, “By implementing confounder control and quantitative profiling, we were able to reveal potential misleading associations between microbial markers and colorectal cancer development, for example driven by intestinal inflammation,” said lead author Jeroen Raes, PI and vice-director at VIB-KU Leuven Center for Microbiology. 

The results have been published in Nature Medicine. The team was from VIB-KU Leuven, UZ Leuven, Janssen Pharmaceutica and multiple international collaborators.

Cancer microbiome research has taken significant strides over the past decade, leading to new insights into biomarkers including in colon cancer. For example, a large-scale prospective study, involving 8,208 participants, used data from the Dutch Microbiome Project with the Dutch nationwide pathology database to identify all recorded cases in that country of colonic biopsies from the last five decades. They linked significant variations in the gut microbiome to pre-cancerous colonic lesions, according to findings presented at UEG Week 2023.

According to the World Health Association, colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 percent of all cancer cases and is the second leading cause of cancer-related deaths worldwide.

This VIB-KU Leuven study underscores the risks of adhering to current methods. In the absence of confounder control, the results were equivalent to those stated by the authors of the published cohorts. However, when confounder control and absolute quantitative methods are incorporated, some previously claimed microbial biomarker associations are revealed to be driven by other factors rather than cancer.

The study identifies transit time, fecal calprotectin, and BMI as primary microbial covariates, surpassing the variance explained by traditional CRC diagnostic groups. Surprisingly, well-established microbiome-CRC targets, such as Fusobacterium nucleatum, fail to significantly associated with CRC diagnostic groups when controlling for these covariates. Instead, the study underscores the robust associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica, and Prevotella intermedia with CRC, highlighting their potential as future targets for intervention.

“This research underscores the importance of rigorous methodologies in unraveling complex disease-microbiome associations. Many of the discovered targets have been mostly ignored until now,” said Raul Yhossef Tito-Tadeo, first author and postdoc at the Raes Lab.

The researchers point out there is a high need for fast, non-invasive colon cancer diagnostics. Current screening tools (e.g based on the presence of blood in stools) are not specific enough and require too many unnecessary colonoscopies, putting extra burden on the heathcare system. 

“Fast, specific stool tests will allow a much larger number of individuals to be screened early, avoiding many unnecessary colon cancer deaths,” said Sabine Tejpar, gastroenterologist at UZ Leuven, head of the digestive oncology group, and professor at the faculty of medicine KU Leuven.

Also of Interest