Importance of Quantitative Microbiome Profiling in CRC Biomarker Discovery

In a paper published in Nature Medicine, microbiome researchers stress the importance of using quantitative methods and extensive confounder control to discover microbiome biomarkers in colorectal cancer development. This rigorous approach challenges previous research that has relied on non-quantitative, descriptive biomarker discovery methods, which may have led to incorrect associations.

The study combined Quantitative Microbiome Profiling (QMP) with extensive patient phenotyping from a group of 589 patients at various stages of colorectal cancer. Additionally, the researchers reanalyzed data from 15 published studies encompassing a total of 4439 patients and controls. Their findings revealed that 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 were incorporated, some previously claimed microbial biomarker associations were revealed to be driven by other factors rather than cancer diagnosis.

"This study shows we must separate the wheat from the chaff when studying cancer-associated biomarkers. 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 Professor Dr. Jeroen Raes, senior author on the paper.

The study identified 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, failed to significantly associate with CRC diagnostic groups when controlling for these covariates. Instead, the study underscored 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 of the paper.

The clinical implications of this study are significant, as Professor Dr. Sabine Tejpar, co-author of the paper, highlighted. "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 unnecessary burden on the healthcare system. Fast, specific stool tests will allow a much larger number of individuals to be screened early, avoiding many unnecessary colon cancer deaths."