Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk

Abstract

Summary 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.

Editorial: the microbiome, aspirin and colorectal cancer

“…A 6‐week 325 mg/d aspirin challenge increased the abundance of Clostridium XIVa, Ruminococcus and Akkermansia and decreased the abundance of Parabacteroides and Dorea ; findings consistent with those of a previous meta‐analysis on gut microbiota patterns in CRC and also resonant with the known anti‐inflammatory and immune‐modulating effects of these taxa and their metabolites 5,6 . Interestingly, following a 6‐week washout, microbial composition in both aspirin and control arms were similar, though different from baseline 5 . Thus, the aspirin effects were short‐lived and reverted to baseline on withdrawal.…”

“…The study by Prizment and colleagues takes these interactions a step forward by identifying links between bacterial taxa associated with CRC and aspirin‐induced changes in microbial diversity 5 . A 6‐week 325 mg/d aspirin challenge increased the abundance of Clostridium XIVa, Ruminococcus and Akkermansia and decreased the abundance of Parabacteroides and Dorea ; findings consistent with those of a previous meta‐analysis on gut microbiota patterns in CRC and also resonant with the known anti‐inflammatory and immune‐modulating effects of these taxa and their metabolites 5,6 . Interestingly, following a 6‐week washout, microbial composition in both aspirin and control arms were similar, though different from baseline 5 .…”

“…Furthermore, some of the observed changes might be explained by confounders such as diet, exposure to other lifestyle factors and comorbid and, perhaps, unidentified disease; not to mention the impact of methodological issues related to microbial analysis 5 . The presence of a control group in this study helped mitigate some of these effects but its short‐term nature precluded the all‐important definition of the longer term effects of aspirin on the microbiome 5 . Could, for example, the microbiome adapt to aspirin over time and lose those signatures associated with cancer prevention?…”

“…Of relevance to the anti‐cancer effects of aspirin, it has recently been shown that a microbial intervention with a probiotic organism, Bifidobacterium breve (Bif195), 7 abrogated aspirin effects on the small intestine. Prizment and colleagues 5 are correct in concluding that the further elucidation of aspirin‐microbial interactions may inform large, longer duration, variable dose studies 8 …”

Letter: synergistic role of gut flora with aspirin to prevent colorectal cancers

“…We read with great interest the paper by Prizment et al about the change of gut microbial composition and bacterial taxa with daily aspirin 325 mg or placebo among healthy volunteers 1 . This showed a potential mechanism for the effect of aspirin in reducing colorectal cancer (CRC) risk and should inspire further studies.…”