Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis

ABSTRACT There is growing evidence that individuals with colonic adenomas and carcinomas harbor a distinct microbiota. Alterations to the gut microbiota may allow the outgrowth of bacterial populations that induce genomic mutations or exacerbate tumor-promoting inflammation. In addition, it is likel...

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Autores principales:	Joseph P. Zackular, Nielson T. Baxter, Grace Y. Chen, Patrick D. Schloss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	16S rRNA gene sequencing azoxymethane colorectal cancer dextran sodium sulfate microbial ecology microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/24f782e4dd9546a3965146a8d0295374
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spelling	oai:doaj.org-article:24f782e4dd9546a3965146a8d02953742021-11-15T15:21:39ZManipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis10.1128/mSphere.00001-152379-5042https://doaj.org/article/24f782e4dd9546a3965146a8d02953742016-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00001-15https://doaj.org/toc/2379-5042ABSTRACT There is growing evidence that individuals with colonic adenomas and carcinomas harbor a distinct microbiota. Alterations to the gut microbiota may allow the outgrowth of bacterial populations that induce genomic mutations or exacerbate tumor-promoting inflammation. In addition, it is likely that the loss of key bacterial populations may result in the loss of protective functions that are normally provided by the microbiota. We explored the role of the gut microbiota in colon tumorigenesis by using an inflammation-based murine model. We observed that perturbing the microbiota with different combinations of antibiotics reduced the number of tumors at the end of the model. Using the random forest machine learning algorithm, we successfully modeled the number of tumors that developed over the course of the model on the basis of the initial composition of the microbiota. The timing of antibiotic treatment was an important determinant of tumor outcome, as colon tumorigenesis was arrested by the use of antibiotics during the early inflammation period of the murine model. Together, these results indicate that it is possible to predict colon tumorigenesis on the basis of the composition of the microbiota and that altering the gut microbiota can alter the course of tumorigenesis. IMPORTANCE Mounting evidence indicates that alterations to the gut microbiota, the complex community of bacteria that inhabits the gastrointestinal tract, are strongly associated with the development of colorectal cancer. We used antibiotic perturbations to a murine model of inflammation-driven colon cancer to generate eight starting communities that resulted in various severities of tumorigenesis. Furthermore, we were able to quantitatively predict the final number of tumors on the basis of the initial composition of the gut microbiota. These results further bolster the evidence that the gut microbiota is involved in mediating the development of colorectal cancer. As a final proof of principle, we showed that perturbing the gut microbiota in the midst of tumorigenesis could halt the formation of additional tumors. Together, alteration of the gut microbiota may be a useful therapeutic approach to preventing and altering the trajectory of colorectal cancer.Joseph P. ZackularNielson T. BaxterGrace Y. ChenPatrick D. SchlossAmerican Society for Microbiologyarticle16S rRNA gene sequencingazoxymethanecolorectal cancerdextran sodium sulfatemicrobial ecologymicrobiomeMicrobiologyQR1-502ENmSphere, Vol 1, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S rRNA gene sequencing azoxymethane colorectal cancer dextran sodium sulfate microbial ecology microbiome Microbiology QR1-502
spellingShingle	16S rRNA gene sequencing azoxymethane colorectal cancer dextran sodium sulfate microbial ecology microbiome Microbiology QR1-502 Joseph P. Zackular Nielson T. Baxter Grace Y. Chen Patrick D. Schloss Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis
description	ABSTRACT There is growing evidence that individuals with colonic adenomas and carcinomas harbor a distinct microbiota. Alterations to the gut microbiota may allow the outgrowth of bacterial populations that induce genomic mutations or exacerbate tumor-promoting inflammation. In addition, it is likely that the loss of key bacterial populations may result in the loss of protective functions that are normally provided by the microbiota. We explored the role of the gut microbiota in colon tumorigenesis by using an inflammation-based murine model. We observed that perturbing the microbiota with different combinations of antibiotics reduced the number of tumors at the end of the model. Using the random forest machine learning algorithm, we successfully modeled the number of tumors that developed over the course of the model on the basis of the initial composition of the microbiota. The timing of antibiotic treatment was an important determinant of tumor outcome, as colon tumorigenesis was arrested by the use of antibiotics during the early inflammation period of the murine model. Together, these results indicate that it is possible to predict colon tumorigenesis on the basis of the composition of the microbiota and that altering the gut microbiota can alter the course of tumorigenesis. IMPORTANCE Mounting evidence indicates that alterations to the gut microbiota, the complex community of bacteria that inhabits the gastrointestinal tract, are strongly associated with the development of colorectal cancer. We used antibiotic perturbations to a murine model of inflammation-driven colon cancer to generate eight starting communities that resulted in various severities of tumorigenesis. Furthermore, we were able to quantitatively predict the final number of tumors on the basis of the initial composition of the gut microbiota. These results further bolster the evidence that the gut microbiota is involved in mediating the development of colorectal cancer. As a final proof of principle, we showed that perturbing the gut microbiota in the midst of tumorigenesis could halt the formation of additional tumors. Together, alteration of the gut microbiota may be a useful therapeutic approach to preventing and altering the trajectory of colorectal cancer.
format	article
author	Joseph P. Zackular Nielson T. Baxter Grace Y. Chen Patrick D. Schloss
author_facet	Joseph P. Zackular Nielson T. Baxter Grace Y. Chen Patrick D. Schloss
author_sort	Joseph P. Zackular
title	Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis
title_short	Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis
title_full	Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis
title_fullStr	Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis
title_full_unstemmed	Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis
title_sort	manipulation of the gut microbiota reveals role in colon tumorigenesis
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/24f782e4dd9546a3965146a8d0295374
work_keys_str_mv	AT josephpzackular manipulationofthegutmicrobiotarevealsroleincolontumorigenesis AT nielsontbaxter manipulationofthegutmicrobiotarevealsroleincolontumorigenesis AT graceychen manipulationofthegutmicrobiotarevealsroleincolontumorigenesis AT patrickdschloss manipulationofthegutmicrobiotarevealsroleincolontumorigenesis
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Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis

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