Effect of Aspirin on Gut Microbiome

The pilot study will evaluate the feasibility of conducting a large randomized trial and estimate the effects of aspirin on the gut microbiome. The study will recruit 50 healthy subjects, 50-75 years old, from the PRospective Evaluation of SEPTin 9 (PRESEPT) cohort living in the greater Twin Cities area. The Primary Aim is to estimate the impact of a 3- and 6-week intake of once daily 325 mg aspirin on the composition of the gut microbiome using a randomized placebo-controlled double-blinded design, i.e. examine the change of microbiome over time within and between the subjects. The hypothesis for this aim is that in the aspirin arm versus the placebo arm, gut microbiome composition will shift towards a lower proportion of pro-inflammatory, CRC-predisposing bacteria (e.g. Fusobacteria) and higher proportion of anti-inflammatory, CRC-protective bacteria (e.g. butyrate-producing bacteria). The Secondary Aims are to examine the correlation between the aspirin-related changes in microbiome profile with the levels of circulating inflammatory biomarkers in urine and plasma. Within-individual and between-arm differences in microbiome composition will be compared after 3 and 6 weeks of aspirin intake. Also, the microbiome composition will be compared after 3-week and 6-week wash-out periods to test whether these periods are sufficient to restore gut microbiome composition to a pre-treatment level. This study will inform future crossover randomized studies focusing on CRC preventive interventions that will enable clinicians to identify optimal candidates for aspirin therapy for the purposes of CRC prevention using this accessible and cheap drug.