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): Jeshudy, Claregrieve1, WikiWorks

Subjects

Location of subjects
Italy
Host species Species from which microbiome was sampled (if applicable)
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
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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with CRC
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
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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

Needs review

Curated date: 2022/08/02

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S1A

Description: Differential microbial abundance between CRC patients and controls

Abundance in Group 1: decreased abundance in CRC

NCBI Quality ControlLinks
Acetohalobium
Arachidicoccus
Asaia
Asaia bogorensis
Asticcacaulis excentricus
Bacteroides ovatus
Barnesiella
Bifidobacterium pseudocatenulatum
Blautia sp.
Caldithrix
Chitinophaga
Chitinophaga pinensis
Clostridioides
Clostridium baratii
Clostridium saccharobutylicum
Clostridium tetani
Crocosphaera subtropica ATCC 51142
Deinococcus deserti
Desulfosporosinus
Eubacterium
Fibrella
Fimbriimonas ginsengisoli
Gilvibacter
Haematospirillum jordaniae
Lachnospira eligens
Lactobacillus jensenii
Limosilactobacillus fermentum
Marinifilum sp.
Megamonas
Megamonas hypermegale
Mesotoga
Mesotoga prima
Nostoc punctiforme
Paenibacillus swuensis
Paeniclostridium
Paeniclostridium sordellii
Pantoea ananatis
Pedobacter
Phocaeicola salanitronis
Planktothrix agardhii
Roseburia hominis
Rubrobacter radiotolerans
Ruminococcus bicirculans (ex Wegman et al. 2014)
Runella
Runella slithyformis
Selenomonas sp. oral taxon 920
Tannerella sp.
Thermincola
Agathobacter rectalis

Revision editor(s): Jeshudy, Claregrieve1

Signature 2

Needs review

Curated date: 2022/08/02

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S1A

Description: Differential microbial abundance between CRC patients and controls

Abundance in Group 1: increased abundance in CRC

NCBI Quality ControlLinks
Abyssicoccus
Abyssicoccus albus
Acidithiobacillus ferrooxidans
Actinomyces
Actinomyces pacaensis
Aerococcus
Aerococcus urinaehominis
Aeromonas
Aeromonas salmonicida
Aeromonas veronii
Aggregatibacter actinomycetemcomitans
Borrelia
Brenneria goodwinii
Buchnera aphidicola
Candidatus Blochmannia
Candidatus Desulfovibrio trichonymphae
Candidatus Doolittlea
Candidatus Doolittlea endobia
Candidatus Hamiltonella
Candidatus Hamiltonella defensa
Candidatus Ishikawaella
Candidatus Ishikawaella capsulata
Candidatus Moranella endobia
Candidatus Pantoea carbekii
Candidatus Riesia pediculicola
Candidatus Sodalis pierantonius
Cedecea
Cedecea neteri
Citrobacter
Citrobacter freundii
Clostridioides difficile
Coxiella
Coxiella endosymbiont of Amblyomma americanum
Cronobacter
Desulfovibrio
Desulfovibrio vulgaris
Dialister
Dialister pneumosintes
Dickeya
Edwardsiella
Edwardsiella ictaluri
Enterobacter
Enterobacter cloacae
Enterococcus thailandicus
Erwinia
Erwinia amylovora
Erwinia billingiae
Escherichia
Escherichia albertii
Escherichia coli
Fusobacterium
Fusobacterium periodonticum
Gemella sp. oral taxon 928
Klebsiella
Klebsiella aerogenes
Klebsiella oxytoca
Klebsiella pneumoniae
Klebsiella variicola
Kosakonia
Kosakonia cowanii
Lacimicrobium alkaliphilum
Lactobacillus gallinarum
Legionella clemsonensis
Leptotrichia
Marinobacter
Micromonospora
Morganella
Morganella morganii
Pasteurella multocida
Pectobacterium
Pectobacterium atrosepticum
Photobacterium damselae
Photorhabdus
Plautia stali symbiont
Proteus vulgaris
Pseudomonas
Pseudomonas aeruginosa
Raoultella
Salmonella
Salmonella enterica
Schaalia meyeri
Serratia
Serratia marcescens
Shewanella
Shewanella japonica
Shigella
Shigella flexneri
Sodalis
Sodalis endosymbiont of Henestaris halophilus
Sodalis praecaptivus
Syntrophus aciditrophicus
Thioploca
Thioploca ingrica
Vibrio campbellii
Vibrio mimicus
Virgibacillus necropolis
Yersinia
Yersinia enterocolitica
Yersinia pestis

Revision editor(s): Jeshudy, Claregrieve1

Experiment 2


Needs review

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

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

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified


Signature 1

Needs review

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Table S1A

Description: Taxonomic classification summary

Abundance in Group 1: increased abundance in adenomas

NCBI Quality ControlLinks
Actinomyces
Actinomycetaceae
Aerococcaceae
Aerococcus
Brochothrix thermosphacta
Gemella
Gemella sp.
Meiothermus
Pseudomonadaceae
Pseudomonas
Rothia dentocariosa
Aerococcus urinae
Pseudomonas tolaasii

Revision editor(s): Jeshudy

Signature 2

Needs review

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Table S1A

Description: Taxonomic classification summary

Abundance in Group 1: decreased abundance in adenomas

NCBI Quality ControlLinks
Arachidicoccus
Arachidicoccus sp.
Bacteroides ovatus
Bernardetia
Bernardetiaceae
Halopseudomonas sabulinigri
Kosmotogaceae
Lachnospira eligens
Limosilactobacillus fermentum
Paenibacillus mucilaginosus
Planktothrix agardhii
Rickettsiales bacterium Ac37b
Nitrobacteraceae

Revision editor(s): Jeshudy

Experiment 3


Needs review

Curated date: 2022/08/01

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
adenomas
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with CRC
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

Needs review

Curated date: 2022/08/02

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Table S1A

Description: Taxonomic classification summary

Abundance in Group 1: increased abundance in CRC

NCBI Quality ControlLinks
Aeromonas
Aeromonas salmonicida
Aeromonas veronii
Brenneria goodwinii
Buchnera
Buchnera aphidicola
Caldithrix abyssi
Candidatus Doolittlea endobia
Candidatus Hamiltonella
Candidatus Moranella endobia
Candidatus Pantoea carbekii
Candidatus Riesia
Candidatus Riesia pediculicola
Candidatus Sodalis pierantonius
Christensenella massiliensis
Citrobacter
Citrobacter freundii
Coxiella
Coxiella endosymbiont of Amblyomma americanum
Cronobacter
Desulfovibrio
Desulfovibrio piger
Desulfovibrio vulgaris
Dickeya
Edwardsiella
Edwardsiella ictaluri
Enterobacter
Enterobacter cloacae
Erwinia
Erwinia amylovora
Escherichia
Escherichia albertii
Escherichia coli
Fusobacterium
Halioglobus
Halioglobus pacificus
Klebsiella
Klebsiella pneumoniae
Klebsiella variicola
Kosakonia
Lacimicrobium alkaliphilum
Legionella clemsonensis
Meiothermus
Morganella
Morganella morganii
Pantoea
Pasteurella multocida
Photorhabdus
Plautia stali symbiont
Pseudomonas aeruginosa
Raoultella
Salmonella
Salmonella enterica
Serratia marcescens
Shewanella
Shewanella japonica
Shigella
Shigella flexneri
Sodalis
Sodalis endosymbiont of Henestaris halophilus
Sodalis praecaptivus
Sphingomonas
Streptococcus thermophilus
Syntrophus aciditrophicus
Thermoanaerobacterium sp. RBIITD
Thioploca
Thioploca ingrica
Vibrio
Vibrio campbellii
Vibrio mimicus
Yersinia
Yersinia enterocolitica
Syntrophus

Revision editor(s): Jeshudy

Signature 2

Needs review

Curated date: 2022/08/02

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Table S1A

Description: Taxonomic classification summary

Abundance in Group 1: decreased abundance in CRC

NCBI Quality ControlLinks
Bifidobacterium pseudocatenulatum
Desulfuromonas
Sulfurihydrogenibium
Sulfurihydrogenibium sp. YO3AOP1
Crocosphaera subtropica ATCC 51142
Caldithrix
Pectobacterium
Marinifilaceae bacterium
Clostridium saccharobutylicum
Klebsiella oxytoca
Pedobacter
Candidatus Arsenophonus lipoptenae
Heyndrickxia coagulans
Mucilaginibacter
Clostridioides
Clostridioides difficile
Paeniclostridium
Moraxella osloensis
Phocaeicola salanitronis
Anaerostipes
Paeniclostridium sordellii
Anaerostipes hadrus
Clostridium chauvoei
Roseburia
Roseburia hominis
Agathobacter rectalis

Revision editor(s): Jeshudy