Microbiome researchers are challenging the prevailing methods in colon cancer biomarker discovery, introducing quantitative approaches and meticulous confounder control to identify microbiome biomarkers linked to colorectal cancer development. This groundbreaking study, conducted by researchers from VIB-KU Leuven, UZ Leuven, Janssen Pharmaceutical, and international collaborators, represents a significant departure from previous non-quantitative, descriptive approaches to biomarker discovery. Published in Nature Medicine, the study sheds light on obscured contributions that may have led to erroneous associations in the past.
Over the last decade, cancer microbiome research has made significant progress, yielding insights into cancer-related biomarkers. However, previous methodologies lacked quantitative rigor, prompting researchers to reevaluate their approaches. By integrating quantitative microbiome profiling (QMP) with comprehensive patient phenotyping, the researchers examined a cohort of 589 patients at different stages of colorectal cancer. Additionally, they reanalyzed data from fifteen published studies involving 4,439 patients and controls.
The findings revealed that without adequate confounder control, previous associations mirrored those reported by the original studies. However, with the incorporation of confounder control and quantitative methods, certain microbial biomarker associations previously linked to cancer diagnosis were found to be influenced by other factors, such as intestinal inflammation.
Professor Dr. Jeroen Rae’s, PI and Vice-Director at VIB-KU Leuven Center for Microbiology and Raga Institute, emphasized the importance of separating genuine associations from spurious ones in biomarker research. The study identified transit time, fecal calprotectin, and BMI as primary microbial covariates, surpassing traditional CRC diagnostic groups in explanatory power. Surprisingly, well-known microbiome-CRC targets like Fusobacterium nucleator showed no significant association with CRC diagnostic groups when controlling for these covariates.
Instead, the study highlighted the robust associations of Anaerococcus vaginalis, Dialyzer pneumocytes, Parvimonas micra, Pepto streptococcus anaerobius, Porphyromonas asaccharolytica, and Prevotella intermedia with CRC, suggesting their potential as future intervention targets.
The rigorous methodologies employed in this research underscore the importance of unraveling complex disease-microbiome associations. Many of the identified targets have been previously overlooked, indicating new avenues for exploration. The study’s clinical implications are significant, particularly in the realm of non-invasive colon cancer diagnostics. Fast, specific stool tests could revolutionize screening methods, potentially reducing unnecessary colonoscopies and preventing many colon cancer deaths.
