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

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/22

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

31530647

DOI Digital object identifier for electronic documents.

10.1128/mSystems.00289-19

URI

Authors

Tarallo S, Ferrero G, Gallo G, Francavilla A, Clerico G, Realis Luc A, Manghi P, Thomas AM, Vineis P, Segata N, Pardini B, Naccarati A, Cordero F

Journal

mSystems

Year

2019

Keywords:

gut microbiome, human stool samples, microRNAs, small RNAs

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.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/22

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): WikiWorks, Claregrieve1, Jeshudy, Peace Sandy, ChiomaBlessing

Subjects

Location of subjects: Italy

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine,Colorectal cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Colorectal cancer (CRC)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with colorectal carcinoma

Group 0 sample size Number of subjects in the control (unexposed) group: 24

Group 1 sample size Number of subjects in the case (exposed) group: 29

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-12

Curated date: 2024/01/12

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental. Table S1B

Description: Differences in fecal microbiome among healthy and carcinoma (CRC) patients

Abundance in Group 1: decreased abundance in Colorectal cancer (CRC)

NCBI	Quality Control	Links
Bacteroides intestinalis
Bifidobacterium adolescentis
Faecalibacterium prausnitzii
Lachnospira eligens
unclassified Subdoligranulum
Bifidobacterium longum

Revision editor(s): ChiomaBlessing

Signature 2

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Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental. Table S1B

Description: Differences in fecal microbiome among healthy and carcinoma (CRC) patients

Abundance in Group 1: increased abundance in Colorectal cancer (CRC)

NCBI	Quality Control	Links
Morganella morganii
Klebsiella oxytoca
Escherichia coli
Leyella stercorea
[Clostridium] symbiosum

Revision editor(s): ChiomaBlessing

Experiment 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): WikiWorks, Jeshudy, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies: Adenomas

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with colorectal adenomas

Group 1 sample size Number of subjects in the case (exposed) group: 27

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): None specified

Lab analysis

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-12

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): Jeshudy, ChiomaBlessing

Source: Supplemental. Table S1B

Description: Differences in fecal microbiome among healthy and adenoma patients

Abundance in Group 1: decreased abundance in Adenomas

NCBI	Quality Control	Links
Akkermansia muciniphila
Lachnospira eligens

Revision editor(s): Jeshudy, ChiomaBlessing

Experiment 3

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-12

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): WikiWorks, Jeshudy, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Adenoma

Group 1 name Corresponds to the case (exposed) group for case-control studies: Carcinoma (CRC)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with colorectal carcinoma