Abstract
Background: Aspirin use is associated with decreased risk of colorectal cancer (CRC), possibly by modulating the gut microbiome. We conducted a pilot double-blind randomized trial to evaluate the effect of aspirin on the gut microbiome. (ClinicalTrials.gov NCT02761486).
Methods: Fifty healthy individuals 50-75 years old were randomized (3:2) to receive a daily standard dose of aspirin (325 mg, N=30) or placebo (lactose, N=20) for 6 weeks followed by a 6-week washout. Stool specimens were collected at baseline, 3, 6, 9, and 12 weeks, and analyzed using 16S ribosomal RNA gene sequencing (V4 region) and Mothur software [ver. 1.35.1]. Fifteen genera associated with CRC were pre-specified from a published meta-analysis of the gut microbiome and CRC [Shah, 2017]. Among these 15 genera, eight genera, which were present in >10% of subjects at baseline in our study, were examined. Additionally, we examined four taxa previously associated with aspirin in a cross-sectional study of non-steroidal anti-inflammatory drugs and the gut microbiome [Rogers, 2016]. Mixed-effects logistic regression was used to estimate associations between aspirin use and changes in the relative abundance of taxa from pre- to post-treatment (baseline to week 6) via an interaction term (treatment*time). Log of odds ratio (β estimate) and P-values for the interaction term comparing aspirin to placebo for week 6 versus baseline are presented.
Results and conclusions. Out of the 8 pre-specified genera found to be associated with CRC in the meta-analysis, the interaction term was significant for 3 genera: Parabacteroides (β =-0.43, P<0.0001), Dorea (β =-1.56, P=0.02), and Akkermansia (β =0.30, P=0.009). These results suggest that aspirin decreases the relative abundance of two bacteria increased in CRC cases compared to non-cases - Parabacteroides and Dorea., while it increases the relative abundance of Akkermansia, which has been associated with anti-cancer immune response and improved survival of CRC patients. The following taxa that were previously associated with aspirin [Rogers, 2016] were also associated with aspirin in the present trial: family Ruminococcaceae (β= 0.33, P<0.0001), genera Bacteroides (β= -0.39; P<0.0001) and Prevotella (β= 0.51; P<0.0001). Our study suggests that aspirin changes the relative abundances of several gut bacteria previously shown to be associated with CRC.
Citation Format: Anna E. Prizment, Jeremiah Menk, Christopher Staley, Sithara Vivek, Guillaume Onyeaghala, Bharat Thyagarajan, Ryan Demmer, Dan Knights, Kathie Meyer, Aasma Shaukat, Alexander Khorutz, Michael J. Sadowsky, Robert J. Straka, Timothy Church. Effect of aspirin on gut microbiome in a pilot randomized double-blind trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5060.
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