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.
Bibliographical noteFunding Information:
The research was supported by the University of Minnesota Grant‐in‐Aid of Research, Artistry, and Scholarship program and the National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.
The research was supported by the University of Minnesota Grant-in-Aid of Research, Artistry, and Scholarship program and the National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences. We are thankful to study coordinators, Jennifer Stromberg and Allison Iwan, and other staff (Jeremiah Menk, Lori Strayer and Frank Strahan) who helped with the study. We thank the University of Minnesota Genomics Center for conducting the genetic analyses (sequencing data were processed and analysed using the resources of the Minnesota Supercomputing Institute); Eicosanoid Core Laboratory, University of Vanderbilt (Ginger Milne) for measuring urine biomarkers; Fairview Investigational Drug Services (Luke Darlette) for preparing treatment capsules; and Epidemiology Clinical Research Center (Margaret Krieser) for providing space for the recruitment of the study subjects. We are also grateful to Michael Franklin, a medical writer, for reviewing the paper. The study was registered using Clinical Trials Registration NCT02761486. Declaration of personal interests: DK serves as CEO of CoreBiome, a company involved in the commercialization of microbiome analysis. CoreBiome is now a wholly owned subsidiary of OraSure. These interests have been reviewed and managed by the University of Minnesota in accordance with its conflict-of-interest policies. All other authors do not have personal interests.
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