Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development
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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
Tito RY, Verbandt S, Aguirre Vazquez M, Lahti L, Verspecht C, Lloréns-Rico V, Vieira-Silva S, Arts J, Falony G, Dekker E, Reumers J, Tejpar S, Raes J
Journal
Nature medicine
Year
2024
Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Subjects
- Location of subjects
- Belgium
- 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
- Controls (CTLs)
- 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 with Colorectal Cancer (CRC)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 205
- Group 1 sample size Number of subjects in the case (exposed) group
- 47
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- 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
- Kruskall-Wallis
- 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 Svetlana up on 2025-3-17
Source: Supplementary Table 7
Description: Differences in relative (RMP) species abundances over diagnostic groups LCMP cohort (n=589, Kruskal-Wallis and adjusted for multiple testing (AdjP, BH method)).
Abundance in Group 1: increased abundance in Colorectal Cancer (CRC)
Revision editor(s): Aleru Divine
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls (CTLs) with normal levels of calprotectin
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Colorectal Cancer (CRC) with normal levels of calprotectin
- Group 0 sample size Number of subjects in the control (unexposed) group
- 112
- Group 1 sample size Number of subjects in the case (exposed) group
- 12
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Source: Supplementary Table 10
Description: Differences in relative (RMP) species abundances over diagnostic groups in LCMP cohort subset with normal levels of fecal calprotectin (n=340 (112 PWoL, 216 PWP and 12 PWT, Kruskal-Wallis and adjusted for multiple testing (AdjP, BH method)).
Abundance in Group 1: increased abundance in Colorectal Cancer (CRC)
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerococcus vaginalis | ||
| Harryflintia acetispora | ||
| Parvimonas micra | ||
| Prevotella intermedia |
Revision editor(s): Aleru Divine
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Polyps (ADE)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Colorectal Cancer (CRC)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 337
- Group 1 sample size Number of subjects in the case (exposed) group
- 47
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Source: Supplementary Table 7
Description: Differences in relative (RMP) species abundances over diagnostic groups LCMP cohort (n=589, Kruskal-Wallis and adjusted for multiple testing (AdjP, BH method)).
Abundance in Group 1: increased abundance in Colorectal Cancer (CRC)
Revision editor(s): Aleru Divine
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Polyps (ADE) with normal levels of calprotectin
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Colorectal Cancer (CRC) with normal levels of calprotectin
- Group 0 sample size Number of subjects in the control (unexposed) group
- 216
- Group 1 sample size Number of subjects in the case (exposed) group
- 12
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-17
Source: Supplementary Table 10
Description: Differences in relative (RMP) species abundances over diagnostic groups in LCMP cohort subset with normal levels of fecal calprotectin (n=340 (112 PWoL, 216 PWP and 12 PWT, Kruskal-Wallis and adjusted for multiple testing (AdjP, BH method)).
Abundance in Group 1: increased abundance in Colorectal Cancer (CRC)
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerococcus vaginalis | ||
| Harryflintia acetispora | ||
| Parvimonas micra | ||
| Prevotella intermedia |
Revision editor(s): Aleru Divine
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