Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples

ABSTRACT Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may...

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Autores principales: Sonia Tarallo, Giulio Ferrero, Gaetano Gallo, Antonio Francavilla, Giuseppe Clerico, Alberto Realis Luc, Paolo Manghi, Andrew Maltez Thomas, Paolo Vineis, Nicola Segata, Barbara Pardini, Alessio Naccarati, Francesca Cordero
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Publicado: American Society for Microbiology 2019
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spelling oai:doaj.org-article:f37f508f65fc4e14be8522387a8395b42021-12-02T18:15:44ZAltered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples10.1128/mSystems.00289-192379-5077https://doaj.org/article/f37f508f65fc4e14be8522387a8395b42019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00289-19https://doaj.org/toc/2379-5077ABSTRACT Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes. IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical tests.Sonia TaralloGiulio FerreroGaetano GalloAntonio FrancavillaGiuseppe ClericoAlberto Realis LucPaolo ManghiAndrew Maltez ThomasPaolo VineisNicola SegataBarbara PardiniAlessio NaccaratiFrancesca CorderoAmerican Society for Microbiologyarticlegut microbiomehuman stool samplessmall RNAsmicroRNAsMicrobiologyQR1-502ENmSystems, Vol 4, Iss 5 (2019)
institution DOAJ
collection DOAJ
language EN
topic gut microbiome
human stool samples
small RNAs
microRNAs
Microbiology
QR1-502
spellingShingle gut microbiome
human stool samples
small RNAs
microRNAs
Microbiology
QR1-502
Sonia Tarallo
Giulio Ferrero
Gaetano Gallo
Antonio Francavilla
Giuseppe Clerico
Alberto Realis Luc
Paolo Manghi
Andrew Maltez Thomas
Paolo Vineis
Nicola Segata
Barbara Pardini
Alessio Naccarati
Francesca Cordero
Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples
description ABSTRACT Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes. IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical tests.
format article
author Sonia Tarallo
Giulio Ferrero
Gaetano Gallo
Antonio Francavilla
Giuseppe Clerico
Alberto Realis Luc
Paolo Manghi
Andrew Maltez Thomas
Paolo Vineis
Nicola Segata
Barbara Pardini
Alessio Naccarati
Francesca Cordero
author_facet Sonia Tarallo
Giulio Ferrero
Gaetano Gallo
Antonio Francavilla
Giuseppe Clerico
Alberto Realis Luc
Paolo Manghi
Andrew Maltez Thomas
Paolo Vineis
Nicola Segata
Barbara Pardini
Alessio Naccarati
Francesca Cordero
author_sort Sonia Tarallo
title Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples
title_short Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples
title_full Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples
title_fullStr Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples
title_full_unstemmed Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples
title_sort altered fecal small rna profiles in colorectal cancer reflect gut microbiome composition in stool samples
publisher American Society for Microbiology
publishDate 2019
url https://doaj.org/article/f37f508f65fc4e14be8522387a8395b4
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