Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

ABSTRACT Disrupted interactions between host and intestinal bacteria are implicated in colorectal cancer (CRC) development. However, activities derived from these bacteria and their interplay with the host are unclear. Here, we examine this interplay by performing mouse and microbiota RNA sequencing...

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Autores principales:	Sarah Tomkovich, Raad Z. Gharaibeh, Christine M. Dejea, Jillian L. Pope, Jinmai Jiang, Kathryn Winglee, Josee Gauthier, Rachel C. Newsome, Ye Yang, Anthony A. Fodor, Thomas D. Schmittgen, Cynthia L. Sears, Christian Jobin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	colorectal cancer transcriptomics microRNAs microbiota biofilm germfree Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b1088a218e284abdb7be9f27d8e4177e
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spelling	oai:doaj.org-article:b1088a218e284abdb7be9f27d8e4177e2021-12-02T18:39:47ZHuman Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer10.1128/mSystems.00451-192379-5077https://doaj.org/article/b1088a218e284abdb7be9f27d8e4177e2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00451-19https://doaj.org/toc/2379-5077ABSTRACT Disrupted interactions between host and intestinal bacteria are implicated in colorectal cancer (CRC) development. However, activities derived from these bacteria and their interplay with the host are unclear. Here, we examine this interplay by performing mouse and microbiota RNA sequencing on colon tissues and 16S and small RNA sequencing on stools from germfree (GF) and gnotobiotic ApcMinΔ850/+;Il10−/− mice associated with microbes from biofilm-positive human CRC tumor (BF+T) and biofilm-negative healthy (BF-bx) tissues. The bacteria in BF+T mice differentially expressed (DE) >2,900 genes, including genes related to bacterial secretion, virulence, and biofilms but affected only 62 host genes. Small RNA sequencing of stools from these cohorts revealed eight significant DE host microRNAs (miRNAs) based on biofilm status and several miRNAs that correlated with bacterial taxon abundances. Additionally, computational predictions suggest that some miRNAs preferentially target bacterial genes while others primarily target mouse genes. 16S rRNA sequencing of mice that were reassociated with mucosa-associated communities from the initial association revealed a set of 13 bacterial genera associated with cancer that were maintained regardless of whether the reassociation inoculums were initially obtained from murine proximal or distal colon tissues. Our findings suggest that complex interactions within bacterial communities affect host-derived miRNA, bacterial composition, and CRC development. IMPORTANCE Bacteria and bacterial biofilms have been implicated in colorectal cancer (CRC), but it is still unclear what genes these microbial communities express and how they influence the host. MicroRNAs regulate host gene expression and have been explored as potential biomarkers for CRC. An emerging area of research is the ability of microRNAs to impact growth and gene expression of members of the intestinal microbiota. This study examined the bacteria and bacterial transcriptome associated with microbes derived from biofilm-positive human cancers that promoted tumorigenesis in a murine model of CRC. The murine response to different microbial communities (derived from CRC patients or healthy people) was evaluated through RNA and microRNA sequencing. We identified a complex interplay between biofilm-associated bacteria and the host during CRC in mice. These findings may lead to the development of new biomarkers and therapeutics for identifying and treating biofilm-associated CRCs.Sarah TomkovichRaad Z. GharaibehChristine M. DejeaJillian L. PopeJinmai JiangKathryn WingleeJosee GauthierRachel C. NewsomeYe YangAnthony A. FodorThomas D. SchmittgenCynthia L. SearsChristian JobinAmerican Society for Microbiologyarticlecolorectal cancertranscriptomicsmicroRNAsmicrobiotabiofilmgermfreeMicrobiologyQR1-502ENmSystems, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer transcriptomics microRNAs microbiota biofilm germfree Microbiology QR1-502
spellingShingle	colorectal cancer transcriptomics microRNAs microbiota biofilm germfree Microbiology QR1-502 Sarah Tomkovich Raad Z. Gharaibeh Christine M. Dejea Jillian L. Pope Jinmai Jiang Kathryn Winglee Josee Gauthier Rachel C. Newsome Ye Yang Anthony A. Fodor Thomas D. Schmittgen Cynthia L. Sears Christian Jobin Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
description	ABSTRACT Disrupted interactions between host and intestinal bacteria are implicated in colorectal cancer (CRC) development. However, activities derived from these bacteria and their interplay with the host are unclear. Here, we examine this interplay by performing mouse and microbiota RNA sequencing on colon tissues and 16S and small RNA sequencing on stools from germfree (GF) and gnotobiotic ApcMinΔ850/+;Il10−/− mice associated with microbes from biofilm-positive human CRC tumor (BF+T) and biofilm-negative healthy (BF-bx) tissues. The bacteria in BF+T mice differentially expressed (DE) >2,900 genes, including genes related to bacterial secretion, virulence, and biofilms but affected only 62 host genes. Small RNA sequencing of stools from these cohorts revealed eight significant DE host microRNAs (miRNAs) based on biofilm status and several miRNAs that correlated with bacterial taxon abundances. Additionally, computational predictions suggest that some miRNAs preferentially target bacterial genes while others primarily target mouse genes. 16S rRNA sequencing of mice that were reassociated with mucosa-associated communities from the initial association revealed a set of 13 bacterial genera associated with cancer that were maintained regardless of whether the reassociation inoculums were initially obtained from murine proximal or distal colon tissues. Our findings suggest that complex interactions within bacterial communities affect host-derived miRNA, bacterial composition, and CRC development. IMPORTANCE Bacteria and bacterial biofilms have been implicated in colorectal cancer (CRC), but it is still unclear what genes these microbial communities express and how they influence the host. MicroRNAs regulate host gene expression and have been explored as potential biomarkers for CRC. An emerging area of research is the ability of microRNAs to impact growth and gene expression of members of the intestinal microbiota. This study examined the bacteria and bacterial transcriptome associated with microbes derived from biofilm-positive human cancers that promoted tumorigenesis in a murine model of CRC. The murine response to different microbial communities (derived from CRC patients or healthy people) was evaluated through RNA and microRNA sequencing. We identified a complex interplay between biofilm-associated bacteria and the host during CRC in mice. These findings may lead to the development of new biomarkers and therapeutics for identifying and treating biofilm-associated CRCs.
format	article
author	Sarah Tomkovich Raad Z. Gharaibeh Christine M. Dejea Jillian L. Pope Jinmai Jiang Kathryn Winglee Josee Gauthier Rachel C. Newsome Ye Yang Anthony A. Fodor Thomas D. Schmittgen Cynthia L. Sears Christian Jobin
author_facet	Sarah Tomkovich Raad Z. Gharaibeh Christine M. Dejea Jillian L. Pope Jinmai Jiang Kathryn Winglee Josee Gauthier Rachel C. Newsome Ye Yang Anthony A. Fodor Thomas D. Schmittgen Cynthia L. Sears Christian Jobin
author_sort	Sarah Tomkovich
title	Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
title_short	Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
title_full	Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
title_fullStr	Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
title_full_unstemmed	Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
title_sort	human colon mucosal biofilms and murine host communicate via altered mrna and microrna expression during cancer
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b1088a218e284abdb7be9f27d8e4177e
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_version_	1718377760276086784

Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

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