If validated by additional research, microbiologists, pathologists, and medical laboratory professionals might soon find analysis of the human microbiome to be a useful marker in screening for colon cancer

Microbiologists may play a greater role in the early detection of colorectal cancer, if the findings of a research study at the University of Michigan (UMich) are confirmed with additional clinical studies.

Combining gut microbiome analysis with traditional risk factors for colorectal cancer—such as body mass index (BMI), age, and race—significantly improved the ability of pathologists to distinguish healthy people from those with precancerous or cancerous lesions, wrote researchers from the UMich in a scholarly paper published in the November 2014 issue in Cancer Prevention Research.

Research findings indicate that gut microbiomes may be a major factor in development of colorectal cancer. However, more research is required to determine if this microbial community has the potential to be clinically useful as screening tool for early-stage disease.

Gut Microbiome Might be Better, Noninvasive Screening Tool Than gFOBT

Colonoscopy has contributed to a decline of colorectal cancer cases in the United States. Yet, because it is an invasive, uncomfortable procedure, many patients opt for the guaiac fecal occult blood test (gFOBT) instead, which is a non-invasive screening tool, but has low sensitivity. This is why use of gut microbiome analysis, also a non-invasive diagnostic test technology, could identify patients who truly need a colonoscopy, noted the researchers.

In developing this test, lead researcher Patrick Schloss, Ph.D., an Associate Professor in the UMich Department of Microbiology & Immunology, and his colleagues characterized the gut microbiomes from stool samples collected from 90 people, in three clinical groups that represent the stages of colorectal cancer development.

Three Groups, Each with 30 People

One group was 30 healthy people. The second group was 30 people with adenomas. The third group was 30 people with carcinomas.

“Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas,” noted the researchers.

Patrick Schloss, Ph.D. (pictured above), an Associate Professor in the University of Michigan Department of Microbiology & Immunology, led research of the composition of gut microbiome’s relationship to development of colorectal cancer. This research may offer complementary, noninvasive screening tool to determine which patients require colonoscopy. (Photo copyright University of Michigan)

Patrick Schloss, Ph.D. (pictured above), an Associate Professor in the University of Michigan Department of Microbiology & Immunology, led research of the composition of gut microbiome’s relationship to development of colorectal cancer. This research may offer complementary, noninvasive screening tool to determine which patients require colonoscopy. (Photo copyright University of Michigan)

Gut Microbiome Populations Could Signal Colon Cancer Development

Schloss and his research team noticed shifts in gut microbial populations that correspond with cancer development as a result of sequencing the V4 region of the 16S rRNA genes present in the samples.

The gene sequencing was done using Illumina’s MiSeq platform, according to a report published by GenomeWeb.com.

The researchers said that there appears to be an increase of pathogenic populations associated with colon tumorigenesis and a concurrent decrease in potentially protective bacteria. The relative abundance of operational taxonomic units (OTUs) could also differentiate healthy people from those with any type of colonic lesion. It could also differentiate between people with adenomas and those with carcinomas.

The researchers assigned reads generated into OTUs based on sequence similarity, and calculated the relative abundance of each OTU. They then compared the microbiome composition of the different groups using logistic regression models.

Differentiating between Healthy People and Individuals with Adenoma

The comparison revealed the relative abundance of different OTUs that vary between healthy people and individuals with adenoma. It also differentiated between healthy people and those with carcinomas. People with adenomas had higher relative abundances of OTUs associated with the Ruminococcaceae, Clostridium, Pseudomonas, and the Porphyromonadaceae than healthy people, but lower relative abundances of OTUs linked with the Bacteroides, Lachnospiraceae, Clostridiales, and other Clostridium groups.

“This has considerable importance in secondary prevention, because screening for early-stage colorectal cancer hinges on the ability to detect early pathologic changes,” wrote Schloss and his colleagues in the Cancer Prevention Research article.

Similarly, people with carcinomas had higher relative abundances of OTUs associated with Fusobacterium, Porphyromonas, Lachnospiraceae, and Enterobacteriaceae  than the healthy control group, and lower relative abundances of OTUs affiliated with the Bacteroides, other Lachnospiraceae groups, and Clostridiales.

Demographics Improve Ability to Identify People Needing Colonoscopy

Schloss’ team also found that demographic data, including age and race and sometimes BMI and gender, also helped to tell the various groups apart. For instance, adding information regarding the abundance of six OTUs to a model that includes age, race, and gender improved its ability to distinguish healthy people from those with any type of colonic lesion. Without that information, the AUC  for the model was 0.754, but after that OTU data was added, it increased to 0.936, noted the GenomicsWeb article.

Additionally, combining gFOBT results to the microbiome-based models improved the ability to tell the patient groups apart even more. Moreover, the addition of BMI to gFOBT and microbiome data had an even greater discriminatory result, producing an AUC of 0.969.

To determine if the state of the gut microbiome could be used as screening tool, the researchers drew on age-specific colorectal cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER) program at the National Cancer Institute.

They designed a preliminary screening tool of five OTUs, which included Clostridiales, Clostridium, Lachnospiraceae, and two Bacteroides OTUs that are more common in healthy people than in those with adenomas. Schloss’ team noted that people with detectable levels of these OTUs are more likely to have a healthy colon and received a negative score on the screening test.

Bayesian Analysis Improves Ability to Predict Adenomas 50-Fold

Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pre-test to post-test probability of adenoma more than 50-fold,” the researchers continued. “For example, the pretest probability in a 65-year-old was 0.17%, and after using the microbiome data this increased to 10.67% (a one in nine chance of having an adenoma).

“Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions,” wrote the researchers. “Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information.”

State of Gut Microbiome May Improve−Not Replace−Other Screening Tests

Composition of the gut microbiome allowed the researchers to identify which study participants had precancerous adenomatous polyps and which study participants had invasive colorectal cancer, explained Schloss in the GenomeWeb.com report. “If our results are confirmed in larger groups of people, adding gut microbiome analysis to other fecal tests may provide an improved, noninvasive way to screen for colorectal cancer. We don’t think that this would ever replace other colorectal cancer screening approaches, rather we see it as complementary,” added Schloss.

Microbiologists, clinical laboratory managers, and pathologists can expect to see similar findings as other researchers investigate the human microbiome and seek to understand its role in different diseases and health conditions. Ongoing advances in gene sequencing technology and software assessment tools will make it easier, faster, and cheaper for researchers to identify greater numbers of organisms in a specimen, and associate those findings with specific diseases.

—By Patricia Kirk

Related Information:

The Human Gut Microbiome as a Screening Tool for Colorectal Cancer

Addition of Gut Microbiome Data Can Improve Colorectal Cancer Screening

Dietary Modulation of the Human Colonie Microbiota: Introducing the Concept of Prebiotics

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