We appreciated the letter by Koulaouzidis and colleagues, which highlights the need for further studies to understand the mechanistic basis for aspirin's effect on colorectal cancer. Alongside their summary of our work (1) in the context of prior studies, they suggest that the effect of aspirin on gut microbiota should be examined. We agree that this is a high priority. As a rationale, they highlight research that shows aspirin appears to alter the gut microbiome to promote bacteria that are anti-inflammatory, thereby reducing colorectal cancer risk (2). We would further add that preclinical studies identify specific microbes that promote a proinflammatory environment, leading to induction of the enzymes that synthesize oncogenic prostaglandins which are inhibited by aspirin. Our group has also demonstrated that aspirin significantly inhibits tumorigenesis in ApcMin/+ mice inoculated with F. nucleatum and adenomas in aspirin users have significantly less Fusobacterium compared with...

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