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

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/22
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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

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 ControlLinks
Bacteroides intestinalis
Bifidobacterium adolescentis
Faecalibacterium prausnitzii
Lachnospira eligens
unclassified Subdoligranulum
Bifidobacterium longum

Revision editor(s): ChiomaBlessing

Signature 2

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: increased abundance in Colorectal cancer (CRC)

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

Revision editor(s): ChiomaBlessing

Experiment 2


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

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 ControlLinks
Akkermansia muciniphila
Lachnospira eligens

Revision editor(s): Jeshudy, ChiomaBlessing

Experiment 3


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

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, 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
Group 0 sample size Number of subjects in the control (unexposed) group
27
Group 1 sample size Number of subjects in the case (exposed) group
29

Lab analysis

Statistical Analysis

Signature 1

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 adenoma and carcinoma (CRC) patients

Abundance in Group 1: increased abundance in Carcinoma (CRC)

NCBI Quality ControlLinks
Odoribacter splanchnicus

Revision editor(s): ChiomaBlessing

Signature 2

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 adenoma and carcinoma (CRC) patients

Abundance in Group 1: decreased abundance in Carcinoma (CRC)

NCBI Quality ControlLinks
Bifidobacterium catenulatum
Collinsella aerofaciens

Revision editor(s): ChiomaBlessing