Abstract
BackgroundColorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Although individuals diagnosed early have a greater than 90 % chance of survival, more than one-third of individuals do not adhere to screening recommendations partly because the standard diagnostics, colonoscopy and sigmoidoscopy, are expensive and invasive. Thus, there is a great need to improve the sensitivity of non-invasive tests to detect early stage cancers and adenomas. Numerous studies have identified shifts in the composition of the gut microbiota associated with the progression of CRC, suggesting that the gut microbiota may represent a reservoir of biomarkers that would complement existing non-invasive methods such as the widely used fecal immunochemical test (FIT).MethodsWe sequenced the 16S rRNA genes from the stool samples of 490 patients. We used the relative abundances of the bacterial populations within each sample to develop a random forest classification model that detects colonic lesions using the relative abundance of gut microbiota and the concentration of hemoglobin in stool.ResultsThe microbiota-based random forest model detected 91.7 % of cancers and 45.5 % of adenomas while FIT alone detected 75.0 % and 15.7 %, respectively. Of the colonic lesions missed by FIT, the model detected 70.0 % of cancers and 37.7 % of adenomas. We confirmed known associations of Porphyromonas assaccharolytica, Peptostreptococcus stomatis, Parvimonas micra, and Fusobacterium nucleatum with CRC. Yet, we found that the loss of potentially beneficial organisms, such as members of the Lachnospiraceae, was more predictive for identifying patients with adenomas when used in combination with FIT.ConclusionsThese findings demonstrate the potential for microbiota analysis to complement existing screening methods to improve detection of colonic lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0290-3) contains supplementary material, which is available to authorized users.
Highlights
Colorectal cancer (CRC) is the second leading cause of death among cancers in the United States
We demonstrate the potential for microbiota analysis to complement fecal immunochemical test (FIT) for improved detection of colonic lesions, especially adenomas
Complementary detection of lesions by FIT and the microbiota We characterized the bacterial communities of stool samples from 490 patients using 16S rRNA gene sequencing
Summary
Colorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Numerous studies have identified shifts in the composition of the gut microbiota associated with the progression of CRC, suggesting that the gut microbiota may represent a reservoir of biomarkers that would complement existing non-invasive methods such as the widely used fecal immunochemical test (FIT). Several members of the gut microbiota have been shown to potentiate both the development and progression of CRC by a variety of mechanisms [14,15,16]. Each of these organisms may play a role in certain cases of CRC, none of them is present in every case. We postulate that no one organism is an effective biomarker on its own and that focusing on a single bacterial population excludes the potential that the microbial etiology of the disease is polymicrobial
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