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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Reviewed Marked as Reviewed by Fatima on 2022/07/3
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Church TR, Demmer RT, Knights D, Meyer KA, Onyeaghala GC, Prizment AE, Sadowsky MJ, Shaukat A, Staley C, Straka RJ, Thyagarajan B, Vivek S
Journal
Ailmentary Pharmacology and Theraputics
Year
2020
Pages:
12
First page:
976
Keywords:
colorectal cancer, aspirin
Background: Aspirin is associated with decreased risk of colorectal cancer (CRC), potentially by modulating the gut microbiome.

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


Reviewed Marked as Reviewed by Fatima on 2022/07/3

Curated date: 2022/05/27

Curator: Jeshudy

Revision editor(s): Jeshudy, Fatima, WikiWorks, 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

Reviewed Marked as Reviewed by Fatima on 2022/07/3

Curated date: 2022/05/27

Curator: Jeshudy

Revision editor(s): Jeshudy

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 ControlLinks
Prevotella
Lachnospira sp.

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/07/3

Curated date: 2022/06/02

Curator: Jeshudy

Revision editor(s): Jeshudy, Peace Sandy

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 ControlLinks
Veillonella
Clostridium sp. DL-VIII

Revision editor(s): Jeshudy, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2022/07/3

Curated date: 2022/05/27

Curator: Jeshudy

Revision editor(s): Jeshudy, Fatima, WikiWorks

Differences from previous experiment shown

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

Reviewed Marked as Reviewed by Fatima on 2022/07/3

Curated date: 2022/05/27

Curator: Jeshudy

Revision editor(s): Jeshudy, Fatima

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 ControlLinks
Akkermansia
Lachnospira sp.
Oscillospiraceae
Prevotella
Faecalibacterium

Revision editor(s): Jeshudy, Fatima

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/07/3

Curated date: 2022/05/27

Curator: Jeshudy

Revision editor(s): Jeshudy, Fatima

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 ControlLinks
Bacteroides
Dorea
Parabacteroides
Ruminococcus

Revision editor(s): Jeshudy, Fatima