Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk
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Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
Aims: To evaluate the effect of aspirin on the gut microbiome in a double-blinded, randomised placebo-controlled pilot trial.
Methods: Healthy volunteers aged 50-75 received a standard dose of aspirin (325 mg, N = 30) or placebo (N = 20) once daily for 6 weeks and provided stool samples every 3 weeks for 12 weeks. Serial measurements of gut microbial community composition and bacterial abundance were derived from 16S rRNA sequences. Linear discriminant analysis of effect size (LEfSe) was tested for between-arm differences in bacterial abundance. Mixed-effect regression with binomial distribution estimated the effect of aspirin use on changes in the relative abundance of individual bacterial taxa via an interaction term (treatment × time).
Results: Over the study period, there were differences in microbial composition in the aspirin vs placebo arm. After treatment, four taxa were differentially abundant across arms: Prevotella, Veillonella, Clostridium XlVa and Clostridium XVIII clusters. Of pre-specified bacteria associated with CRC (n = 8) or aspirin intake (n = 4) in published studies, interactions were significant for four taxa, suggesting relative increases in Akkermansia, Prevotella and Ruminococcaceae and relative decreases in Parabacteroides, Bacteroides and Dorea in the aspirin vs placebo arm.
Conclusion: Compared to placebo, aspirin intake influenced several microbial taxa (Ruminococcaceae, Clostridium XlVa, Parabacteroides and Dorea) in a direction consistent with a priori hypothesis based on their association with CRC. This suggests that aspirin may influence CRC development through an effect on the gut microbiome. The findings need replication in a larger trial.
Experiment 1
Curated date: 2022/05/27
Curator: Jeshudy
Revision editor(s): WikiWorks, Fatima, Jeshudy, Peace Sandy
Subjects
- Location of subjects
- United States of America
- 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
- Colon Hindgut,Large bowel,Posterior intestine,Colon,colon
- 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
- Placebo
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Aspirin
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Experimental group took 325 mg daily aspirin over six weeks, with additional six weeks of washout
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 30
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months
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
- LEfSe
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.0
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Source: Table 3
Description: Linear discriminant analysis (LDA) effect size (LEfSe) in samples collected after treatment (week 6)
Abundance in Group 1: increased abundance in Aspirin
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Lachnospira sp. |
Revision editor(s): Jeshudy
Signature 2
Source: Table 3
Description: Linear discriminant analysis (LDA) effect size (LEfSe) in samples collected after treatment (week 6)
Abundance in Group 1: decreased abundance in Aspirin
| NCBI | Quality Control | Links |
|---|---|---|
| Veillonella | ||
| Clostridium sp. DL-VIII |
Revision editor(s): Jeshudy, Peace Sandy
Experiment 2
Subjects
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Statistical test
- Mixed-Effects Regression
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
Signature 1
Source: Table 4, text
Description: Regression coefficients (β) and P-values for the interaction term comparing the abundance of pre-specified faecal bacterial taxa in aspirin to placebo arm after 3 weeks (upper row) and 6 weeks (lower row) of treatment vs baseline, the ASMIC study
Abundance in Group 1: increased abundance in Aspirin
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Lachnospira sp. | ||
| Oscillospiraceae | ||
| Prevotella | ||
| Faecalibacterium |
Signature 2
Source: Table 4, text
Description: Regression coefficients (β) and P-values for the interaction term comparing the abundance of pre-specified faecal bacterial taxa in aspirin to placebo arm after 3 weeks (upper row) and 6 weeks (lower row) of treatment vs baseline, the ASMIC study
Abundance in Group 1: decreased abundance in Aspirin
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Dorea | ||
| Parabacteroides | ||
| Ruminococcus |
