Analysis of the gut’s bacterial composition may aid in the noninvasive screening for early-stage colorectal cancer (CRC), according to a study published Aug. 7 in Cancer Prevention Research. The ability of gut bacterial markers to differentiate healthy individuals from those with early- or advanced-stage CRC can be used as a complement to existing screening methods, the authors say.
“The feasibility, lack of invasive procedures, ability to be [a] complement [to] existing screening methods (e.g., gFOBT), and the strength of signal seen in this study support the further investigation and application of microbial biomarkers from stool as a method for colorectal cancer screening,” write the authors, including senior study author Patrick D. Schloss, Ph.D., from the University of Michigan in Ann Arbor. He adds in a statement, “We don’t think that this would ever replace other CRC screening approaches, rather we see it as complementary.”
The researchers used sequencing techniques to characterize the gut microbiome from stool samples in patients across the spectrum of CRC, including those that were healthy (n = 30), with adenoma (n = 30), and with carcinoma (n = 30). Using the Illumina MiSeq platform the researchers analyzed the V4 region of the 16S rRNA gene from the feces of each individual. During the discovery analysis, sequences were categorized into operational taxonomic units (OTU) using a similarity cutoff of 97 percent and then the relative abundance of each OTU was calculated.
Analysis of 25,953 sequences per stool sample showed both an enrichment and depletion of multiple bacterial populations for both adenomas and carcinomas. Data from the gut microbiome (five OTUs for adenomas and six OTUs for carcinomas) when combined with known clinical risk factors of colorectal cancer (fecal occult blood testing [FOBT] results) and demographic (body mass index, age, race), significantly improved the ability to differentiate between healthy and adenoma individuals (4.5-fold), and healthy and carcinoma individuals (5.4-fold), compared to utilizing risk factors alone.
“Interestingly, when we looked at each patient, we rarely observed significant enrichment of every bacterial population among the OTUs incorporated in the logit models,” the authors write. “This strongly suggests that there may be multiple underlying mechanisms by which the microbiome is involved in colorectal cancer.”
Incorporating age-specific incidence rates of colorectal cancer into Bayesian models, the authors found that using gut microbiome data as a screening tool improved the pretest-to-posttest probability of adenoma more than 50-fold. For instance, the pretest probability in a 65-year-old was 0.17 percent, but by incorporating the microbiome data, this probability increased to nearly a one in nine chance of having an adenoma.
The authors say that the significant difference in the gut microbiome of people with colonic adenomas compared with those with healthy colons is of “considerable importance” for screening for early-stage colorectal cancer.
Schloss tells DTET that within the next five years he anticipates microbiome analysis to move into the clinical diagnostic realm, even outside of cancer.
“My dream,” Schloss says, “is that every year at a checkup you take a stool sample, it is sent for sequencing and analysis, and in two weeks the physician calls you and says that you have a high level of this bacteria which is associated with XYZ, and therefore we should consider some more follow-up.”
Schloss says right now the biggest limitation to that scenario is that knowledge of the natural biology of the microbiome is limited and clinicians don’t know how to get rid of a certain deleterious bacteria or why it is there.
Takeaway: Analysis of microbiome markers from stool samples is feasible as a noninvasive screening test for CRC.
