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

• Published in: Alimentary pharmacology & therapeutics 2020-09, Vol.52 (6), p.976-987
• Main Authors: Prizment, Anna E., Staley, Christopher, Onyeaghala, Guillaume C., Vivek, Sithara, Thyagarajan, Bharat, Straka, Robert J., Demmer, Ryan T., Knights, Dan, Meyer, Katie A., Shaukat, Aasma, Sadowsky, Michael J., Church, Timothy R.
• Format: Article
• Language: English
• Subjects: Abundance; Aged; Aspirin; Aspirin - pharmacology; Bacteria; Bacteria - isolation & purification; Binomial distribution; Clostridium; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - prevention & control; Community composition; Discriminant analysis; Double-Blind Method; Female; Gastrointestinal Microbiome - drug effects; Humans; Intestinal microflora; Male; Microbiomes; Microbiota; Microorganisms; Middle Aged; Parabacteroides; Pilot Projects; Prevotella; RNA, Ribosomal, 16S - genetics; rRNA 16S; Ruminococcaceae
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.16013

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.