Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions
Open accessAbstract
BACKGROUND: Colorectal 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). METHODS: We 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. RESULTS: The 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. CONCLUSIONS: These findings demonstrate the potential for microbiota analysis to complement existing screening methods to improve detection of colonic lesions.
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Adding stool microbiome data to risk-factor model scores or to screening tests like FOBT and FIT improves detection accuracy for advanced adenomas.
“Combining the fecal microbiome data with scores from risk factor-based models or results of screening tests (such as fecal occult blood test and fecal immunochemical test) increases the accuracy of detection for advanced adenomas.35, 186, 187”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [187]
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Cites
DeLong, E. R., DeLong, D. M., & Clarke-Pearson, D. L. (1988) · Biometrics · doi:10.2307/2531595 · Cited by 22,649 · see citing works
Schloss, P. D., Westcott, S. L., Ryabin, T., Hall, J. R., Hartmann, M., Hollister, E. B., Lesniewski, R. A., Oakley, B. B., Parks, D. H., Robinson, C. J., et al. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01541-09 · Cited by 20,966 · see citing works
Self-citationNaive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 19,946 · see citing works
Classification and Regression by randomForest
Liaw, A. I., & Wiener, M. C. (2007) · Cited by 18,594 · see citing works
pROC: an open-source package for R and S+ to analyze and compare ROC curves
Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.-C., & Müller, M. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-77 · Cited by 13,697 · see citing works
Kozich, J. J., Westcott, S. L., Baxter, N. T., Highlander, S. K., & Schloss, P. D. (2013) · Applied and Environmental Microbiology · doi:10.1128/aem.01043-13 · Cited by 7,004 · see citing works
Self-citationVEGAN, a package of R functions for community ecology
Dixon, P. M. (2003) · Journal of Vegetation Science · doi:10.1111/j.1654-1103.2003.tb02228.x · Cited by 6,783 · see citing works
Kostic, A. D., Chun, E., Robertson, L., Glickman, J. N., Gallini, C. A., Michaud, M., Clancy, T. E., Chung, D. C., Lochhead, P., Hold, G. L., et al. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.07.007 · Cited by 2,718 · see citing works
Colorectal cancer statistics, 2014
Siegel, R. L., Desantis, C. E., & Jemal, A. (2014) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21220 · Cited by 2,558 · see citing works
Intestinal inflammation targets cancer-inducing activity of the microbiota
Arthur, J. C., Perez-Chanona, E., Mühlbauer, M., Tomkovich, S., Uronis, J. M., Fan, T.-J., Campbell, B. J., Abujamel, T., Dogan, B., Rogers, A. B., et al. (2012) · Science · doi:10.1126/science.1224820 · Cited by 2,263 · see citing works
Genomic analysis identifies association of <i>Fusobacterium</i> with colorectal carcinoma
Kostic, A. D., Gevers, D., Pedamallu, C. S., Michaud, M., Duke, F., Earl, A. M., Ojesina, A. I., Jung, J., Bass, A. J., Tabernero, J., et al. (2012) · Genome Research · doi:10.1101/gr.126573.111 · Cited by 1,960 · see citing works
Multitarget Stool DNA Testing for Colorectal-Cancer Screening
Imperiale, T. F., Ransohoff, D. F., Itzkowitz, S. H., Levin, T. R., Lavin, P., Lidgard, G. P., Ahlquist, D. A., & Berger, B. M. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1311194 · Cited by 1,900 · see citing works
Wu, S., Rhee, K.-J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H.-R., Huso, D. L., Brancati, F. L., Wick, E., McAllister, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2015 · Cited by 1,812 · see citing works
Gut microbiome development along the colorectal adenoma-carcinoma sequence
Feng, Q., Liang, S., Jia, H., Stadlmayr, A., Tang, L., Lan, Z., Zhang, D., Xia, H., Xu, X., Jie, Z., et al. (2015) · Nature Communications · doi:10.1038/ncomms7528 · Cited by 1,506 · see citing works
American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008
Rex, D. K., Johnson, D. A., Anderson, J. C., Schoenfeld, P. S., Burke, C. A., & Inadomi, J. M. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.104 · Cited by 1,397 · see citing works
Potential of fecal microbiota for early-stage detection of colorectal cancer
Zeller, G., Tap, J., Voigt, A. Y., Sunagawa, S., Kultima, J. R., Costea, P. I., Amiot, A., Böhm, J., Brunetti, F., Habermann, N., et al. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145645 · Cited by 1,375 · see citing works
Butyrate inhibits inflammatory responses through NFκB inhibition: implications for Crohn's disease
Segain, J.-P., de la Blétière, D. R., Bourreille, A., Leray, V., Gervois, N., Rosales, C., Ferrier, L., Bonnet, C., Blottière, H. M., & Galmiche, J.-P. (2000) · Gut · doi:10.1136/gut.47.3.397 · Cited by 1,325 · see citing works
The microbiology of butyrate formation in the human colon
Pryde, S. E., Duncan, S. H., Hold, G. L., Stewart, C. S., & Flint, H. J. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11467.x · Cited by 1,320 · see citing works
Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers
Wang, T., Cai, G., Qiu, Y., Fei, N., Zhang, M., Pang, X., Jia, W., Cai, S., & Zhao, L. (2012) · The ISME Journal · doi:10.1038/ismej.2011.109 · Cited by 1,287 · see citing works
Yu, J. Q., Feng, Q., Wong, S. H., Zhang, D., Liang, Q. Y., Qin, Y., Tang, L., Zhao, H., Stenvang, J., Li, Y., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309800 · Cited by 1,259 · see citing works
Human Intestinal Lumen and Mucosa-Associated Microbiota in Patients with Colorectal Cancer
Chen, W., Liu, F., Ling, Z., Tong, X., & Xiang, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039743 · Cited by 1,028 · see citing works
Dynamics and associations of microbial community types across the human body
Ding, T., & Schloss, P. D. (2014) · Nature · doi:10.1038/nature13178 · Cited by 885 · see citing works
Self-citationThe Gut Microbiome Modulates Colon Tumorigenesis
Zackular, J. P., Baxter, N. T., Iverson, K. D., Sadler, W. D., Petrosino, J. F., Chen, G., & Schloss, P. D. (2013) · mBio · doi:10.1128/mbio.00692-13 · Cited by 717 · see citing works
Self-citationThe human gut microbiome as a screening tool for colorectal cancer
Zackular, J. P., Rogers, M. A. M., Ruffin, M. T., & Schloss, P. D. (2014) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0129 · Cited by 551 · see citing works
Self-citationGallimidi, A. B., Fischman, S. L., Revach, B., Bulvik, R., Maliutina, A., Rubinstein, A. M., Nussbaum, G., & Elkin, M. (2015) · Oncotarget · doi:10.18632/oncotarget.4209 · Cited by 426 · see citing works
Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas
Shen, X. J., Rawls, J. F., Randall, T. A., Burcall, L., Mpande, C., Jenkins, N., Jovov, B., Abdo, Z., Sandler, R. S., & Keku, T. O. (2010) · Gut Microbes · doi:10.4161/gmic.1.3.12360 · Cited by 418 · see citing works
Hague, A., Elder, D. J. E., Hicks, D. J., & Paraskeva, C. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910600322 · Cited by 414 · see citing works
Vital signs: colorectal cancer screening test use--United States, 2012.
(2013) · PubMed Central · Cited by 386 · see citing works
Co-occurrence of anaerobic bacteria in colorectal carcinomas
Warren, R. L., Freeman, D. J., Pleasance, S., Watson, P., Moore, R. A., Cochrane, K., Allen-Vercoe, E., & Holt, R. A. (2013) · Microbiome · doi:10.1186/2049-2618-1-16 · Cited by 348 · see citing works
Comparative Evaluation of Immunochemical Fecal Occult Blood Tests for Colorectal Adenoma Detection
Hundt, S., Haug, U., & Brenner, H. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-3-200902030-00005 · Cited by 330 · see citing works
Patient-Reported Barriers to Colorectal Cancer Screening
Jones, R. M., Devers, K. J., Kuzel, A. J., & Woolf, S. H. (2010) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2010.01.021 · Cited by 324 · see citing works
Chen, H.-M., Yu, Y.-N., Wang, J.-L., Lin, Y.-W., Kong, X., Yang, C.-Q., Yang, L., Liu, Z.-J., Yuan, Y.-Z., Liu, F., et al. (2013) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.046607 · Cited by 321 · see citing works
Estimation and Comparison of Receiver Operating Characteristic Curves
PEPE, M. S., Longton, G., & Janes, H. (2009) · The Stata Journal Promoting communications on statistics and Stata · doi:10.1177/1536867x0900900101 · Cited by 306 · see citing works
Schubert, A. M., Sinani, H., & Schloss, P. D. (2015) · mBio · doi:10.1128/mbio.00974-15 · Cited by 269 · see citing works
Self-citationHeitman, S. J., Ronksley, P. E., Hilsden, R. J., Manns, B., Rostom, A., & Hemmelgarn, B. R. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.05.032 · Cited by 258 · see citing works
Hsia, J. A., Kemper, E., Kiefe, C. I., Zapka, J. G., Sofaer, S., Pettinger, M. B., Bowen, D. J., Limacher, M. C., Lillington, L. M., & Mason, E. D. (2000) · Preventive Medicine · doi:10.1006/pmed.2000.0697 · Cited by 253 · see citing works
AUC-RF: A New Strategy for Genomic Profiling with Random Forest
Calle, M. L., Urrea, V., Boulesteix, A., & Malats, N. (2011) · Human Heredity · doi:10.1159/000330778 · Cited by 138 · see citing works
Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model
D’Argenio, G., Cosenza, V., Cave, M. D., Iovino, P., Valle, N. D., Lombardi, G., & Mazzacca, G. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8964397 · Cited by 136 · see citing works
Impact of Colonoscopy Bowel Preparation on Intestinal Microbiota
O'Brien, C. L., Allison, G. E., Grimpen, F., & Pavli, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062815 · Cited by 114 · see citing works
Levi, Z., Rozen, P., Hazazi, R., Vilkin, A., Waked, A., Maoz, E., Birkenfeld, S., Lieberman, N., Klang, S. H., & Niv, Y. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.14 · Cited by 77 · see citing works
Symonds, E. L., Osborne, J. M., Cole, S. R., et al. (2015) · Journal of Medical Screening · doi:10.1177/0969141315584783 · Cited by 67 · see citing works
Grynberg, P., Abeel, T., Lopes, P., et al. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-s11-a1 · Cited by 59 · see citing works
Kapidzic, A., van der Meulen, M. P., Hol, L., et al. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.02.023 · Cited by 44 · see citing works
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Thomas, A. M., Manghi, P., Asnicar, F., Pasolli, E., Armanini, F., Zolfo, M., Beghini, F., Manara, S., Karcher, N., Pozzi, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0405-7 · Cited by 1,030 · see citing works
Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer
Song, M., Chan, A. T., & Sun, J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.06.048 · Cited by 752 · see citing works
The oral microbiota in colorectal cancer is distinctive and predictive
Flemer, B., Warren, R. D., Barrett, M. P., Cisek, K., Das, A., Jeffery, I. B., Hurley, E., O‘Riordain, M., Shanahan, F., & O‘Toole, P. W. (2018) · Gut · doi:10.1136/gutjnl-2017-314814 · Cited by 646 · see citing works
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Sze, M. A., & Schloss, P. D. (2016) · mBio · doi:10.1128/mbio.01018-16 · Cited by 600 · see citing works
Self-citationAlterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes
Nakatsu, G., Zhou, H., Wu, W. K. K., Wong, S. H., Coker, O. O., Dai, Z., Li, X., Szeto, C.-H., Sugimura, N., Lam, T. Y.-T., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.04.018 · Cited by 386 · see citing works
Drewes, J. L., White, J. R., Dejea, C. M., Fathi, P., Iyadorai, T., Vadivelu, J., Roslani, A. C., Wick, E. C., Mongodin, E. F., Loke, M. F., et al. (2017) · npj Biofilms and Microbiomes · doi:10.1038/s41522-017-0040-3 · Cited by 335 · see citing works
Wong, S. H., Kwong, T. N. Y., Chow, T.-C., Luk, A. K. C., Dai, R. Z. W., Nakatsu, G., Lam, T. Y. T., Zhang, L., Wu, J. C. Y., Chan, F. K. L., et al. (2017) · Gut · doi:10.1136/gutjnl-2016-312766 · Cited by 310 · see citing works
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Hannigan, G. D., Duhaime, M. B., Ruffin, M. T., Koumpouras, C. C., & Schloss, P. D. (2018) · mBio · doi:10.1128/mbio.02248-18 · Cited by 298 · see citing works
Problems with the concept of gut microbiota dysbiosis
Brüssow, H. (2020) · Microbial Biotechnology · doi:10.1111/1751-7915.13479 · Cited by 250 · see citing works
Shah, M. S., DeSantis, T. Z., Weinmaier, T., McMurdie, P. J., Cope, J. L., Altrichter, A., Yamal, J.-M., & Hollister, E. B. (2018) · Gut · doi:10.1136/gutjnl-2016-313189 · Cited by 180 · see citing works
Nishiwaki, H., Ito, M., Hamaguchi, T., Maeda, T., Kashihara, K., Tsuboi, Y., Ueyama, J., Yoshida, T., Hanada, H., Takeuchi, I., et al. (2022) · npj Parkinson's Disease · doi:10.1038/s41531-022-00328-5 · Cited by 116 · see citing works
Greathouse, K. L., White, J. R., Padgett, R. N., Perrotta, B. G., Jenkins, G. D., Chia, N., & Chen, J. (2019) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2018-000247 · Cited by 35 · see citing works
- Authors
- Baxter, N. T., Ruffin, M. T., Rogers, M. A. M., & Schloss, P. D.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Schloss, Patrick D.
- Venue
- Genome Medicine
- Published
- 2016-04-06
- Volume
- 8
- Issue
- 1
- Pages
- 37-37
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC4823848
- OpenAlex
- W2314413252
- Cited by
- 354
- References
- 44
- Citations by year
- 2026: 26 · 2025: 27 · 2024: 36 · 2023: 35 · 2022: 52 · 2021: 52 · 2020: 36 · 2019: 34 · 2018: 26 · 2017: 22 · 2016: 7
- FWCI
- 15.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Cancer Institute (U01CA86400)
- National Institute of General Medical Sciences (R01GM099514)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- colorectal cancer, colorectal adenoma, fecal immunochemical test, gut microbiota, random forest classification, non-invasive cancer screening, 16S rRNA gene sequencing, Fusobacterium nucleatum, Lachnospiraceae, Porphyromonas asaccharolytica, Peptostreptococcus stomatis, Parvimonas micra, early cancer detection
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Aged, 80 and over, Colonic Diseases, Feces, Female, Humans, Immunochemistry, Male, Middle Aged, Models, Biological, Occult Blood, RNA, Ribosomal, 16S, ROC Curve, Sensitivity and Specificity, Reproducibility of Results, Sequence Analysis, DNA, Microbiota
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