Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yao J, Yan X, Li Y, Chen Y, Xiao X, Zhou S, Zhang W, Wang L, Chen M, Zeng F, Li Y
Journal
Frontiers in microbiology
Year
2023
Keywords:
16S rRNA, functional constipation, gut microbiota, microRNA, microRNA sequencing
While dysbiosis within the intestinal ecosystem has been associated with functional constipation (FC), the mechanisms underlying the interactions between FC and the microbiome remain poorly elucidated. Recent investigations suggested that host microRNAs (miRNAs) can modulate bacterial growth and influence the composition of the gut microbiome. To explore the connection between gut microbiota and fecal miRNAs in FC patients, we initially employed 16S rRNA sequencing to assess the gut microbial landscape in 30 FC patients and 30 healthy controls (HCs). The α-diversity within the FC group exhibited some alterations, and the β-diversity significantly differed, signifying distinctive variations in gut microbiota composition between FC patients and HCs. Subsequently, we identified 44 differentially expressed (DE) miRNAs in feces from FC patients and HCs. Through correlation analysis between DE miRNAs and FC-associated microbiota, we detected an interaction involving nine DE miRNAs (miR-205-5p, miR-493-5p, miR-215-5p, miR-184, miR-378c, miR-335-5p, miR-514a-3p, miR-141-3p, and miR-34c-5p) with seven bacterial genera (Oscillibacter, Escherichia.Shigella, UCG.002, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG.010, Eubacterium_ruminantium_group and Megamonas), as evidenced by a co-occurrence network. Further, a comprehensive panel of seven diagnostic biomarkers (Oscillibacter, Escherichia.Shigella, UCG.002, miR-205-5p, miR-493-5p, miR-215-5p, and Lachnospiraceae_NK4A136_group) demonstrated robust discriminatory capacity in predicting FC status when integrated into a random forest model (AUC = 0.832, 95% CI: 65.73-98.88). Microbiomes correlating with DE miRNAs exhibited enrichment in distinct predicted metabolic categories. Moreover, miRNAs correlated with FC-associated bacteria were found to be enriched in signaling pathways linked to colonic contractility, including Axon guidance, PI3K-Akt signaling pathway, MAPK signaling pathway, and Hippo signaling pathway. Our study offers a comprehensive insight into the global relationship between microbiota and fecal miRNAs in the context of FC, presenting potential targets for further experimental validation and therapeutic interventions.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Subjects
- Location of subjects
- China
- 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
- Chronic constipation Chronic constipation,Infrequent bowel movements,chronic constipation
- 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
- Functional constipation (FC) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients diagnosed with functional constipation (FC)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 30
- Group 1 sample size Number of subjects in the case (exposed) group
- 30
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- 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
- T-Test
- 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)?
- No
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex, body mass index
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 2A
Description: Differentially abundant taxa between Functional constipation (FC) group and Healthy Controls (HC)
Abundance in Group 1: increased abundance in Functional constipation (FC) group
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 2A
Description: Differentially abundant taxa between Functional constipation (FC) group and Healthy Controls (HC)
Abundance in Group 1: decreased abundance in Functional constipation (FC) group
| NCBI | Quality Control | Links |
|---|---|---|
| Megamonas | ||
| Collinsella | ||
| ML635J-40_aquatic_groupML635J-40_aquatic_group |
Revision editor(s): Tosin
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Statistical test
- LEfSe
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 3.5
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 2B. 2C
Description: Differentially abundant taxa between Functional constipation (FC) group and Healthy Controls (HC)
Abundance in Group 1: increased abundance in Functional constipation (FC) group
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 2B, 2C
Description: Differentially abundant taxa between Functional constipation (FC) group and Healthy Controls (HC)
Abundance in Group 1: decreased abundance in Functional constipation (FC) group
| NCBI | Quality Control | Links |
|---|---|---|
| Selenomonadaceae | ||
| Megamonas | ||
| Prevotellaceae bacterium | ||
| Megamonas funiformis | ||
| Coriobacteriia | ||
| Coriobacteriales |
Revision editor(s): Tosin
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low Bristol stool form scale (BSFS) scores
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High Bristol stool form scale (BSFS) scores
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with exertion in defecation and dry stool at baseline of a high Bristol stool form scale (BSFS)
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
- Statistical test
- Spearman Correlation
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators.
Abundance in Group 1: increased abundance in High Bristol stool form scale (BSFS) scores
| NCBI | Quality Control | Links |
|---|---|---|
| Parabacteroides |
Revision editor(s): Tosin
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Health-related quality of life measurement HRQOL,Health-related quality of life measurement,health-related quality of life measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low Patient-Assessment of Constipation Quality of Life (PAC_QOL)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High Patient-Assessment of Constipation Quality of Life (PAC_QOL)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with High levels of Patient-Assessment of Constipation Quality of Life (PAC_QOL)
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators.
Abundance in Group 1: increased abundance in High Patient-Assessment of Constipation Quality of Life (PAC_QOL)
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae bacterium NK4A136 | ||
| Colidextribacter |
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators.
Abundance in Group 1: decreased abundance in High Patient-Assessment of Constipation Quality of Life (PAC_QOL)
| NCBI | Quality Control | Links |
|---|---|---|
| Megamonas |
Revision editor(s): Tosin
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Constipation Constipation,Costiveness,Dyschezia,constipation
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low levels of straining during defecation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High levels of straining during defecation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with high levels of straining during defecation
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators.
Abundance in Group 1: increased abundance in High levels of straining during defecation
| NCBI | Quality Control | Links |
|---|---|---|
| Flavonifractor | ||
| Oscillibacter | ||
| Bacteroides |
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators.
Abundance in Group 1: decreased abundance in High levels of straining during defecation
| NCBI | Quality Control | Links |
|---|---|---|
| Barnesiella | ||
| Escherichia/Shigella sp. | ||
| Eubacterium ruminantium | ||
| Megamonas | ||
| UCG-010UCG-010 |
Revision editor(s): Tosin
Experiment 6
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Bowel dysfunction disease of lower digestive tract,lower digestive tract disease,Bowel dysfunction,bowel dysfunction
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low levels of Average complete spontaneous bowel movements (CSBM)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High levels of Average complete spontaneous bowel movements (CSBM)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with High frequency of Average complete spontaneous bowel movements (CSBMs) ≤ 2 times per week, which lasted for more than 3 months
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators.
Abundance in Group 1: decreased abundance in High levels of Average complete spontaneous bowel movements (CSBM)
| NCBI | Quality Control | Links |
|---|---|---|
| UCG-010UCG-010 | ||
| Escherichia/Shigella sp. | ||
| Lachnospiraceae UCG-010Lachnospiraceae UCG-010 |
Revision editor(s): Tosin
Experiment 7
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low levels of spontaneous bowel movement (SBM)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High levels of spontaneous bowel movement (SBM)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with High levels of spontaneous bowel movement (SBM)
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators
Abundance in Group 1: decreased abundance in High levels of spontaneous bowel movement (SBM)
| NCBI | Quality Control | Links |
|---|---|---|
| UCG 002UCG 002 | ||
| UCG 005UCG 005 | ||
| UCG 010UCG 010 | ||
| Lachnospiraceae UCG 010Lachnospiraceae UCG 010 | ||
| Escherichia/Shigella sp. |
Revision editor(s): Tosin
Experiment 8
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Depressive disorder depression,melancholia,melancholias,mental depression,syndrome, depressive,syndromes, depressive,Depressive disorder,depressive disorder
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low levels of self-rating depression scale (SDS)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High levels of self-rating depression scale (SDS)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with mental disorder (depression) of a high self-rating depression scale (SDS) standard score
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-29
Source: Figure 4, Table S2
Description: Heatmap showing bacterial genera that were significantly correlated with the constipated-indicators
Abundance in Group 1: decreased abundance in High levels of self-rating depression scale (SDS)
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae UCG 010Lachnospiraceae UCG 010 |
Revision editor(s): Tosin
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