Influence of Aspirin on Human Gut Microbiota Composition and Metabolome

Colorectal cancer (CRC) is the third most common cancer type in males and the second in females, accounting for about 693,900 deaths worldwide per year. Although the annual CRC mortality rate is still very high, it demonstrated a decline by 47% among men and 44% among women from 1990 to 2015. This decreasing trend may be attributed to improved screening, early detection as well as combined CRC treatment. In fact, the mortality rate is expected to reduce further by long-term use of chemopreventive agents that can prevent the development of neoplasms in the large bowel. Several decades of research both in clinic and laboratory has identified aspirin as an effective synthetic CRC chemoprevention drug. It is commonly accepted that aspirin exerts its chemopreventive effects by inhibiting catalytic enzymes cyclooxygenase (COX) -1 and COX-2 involved in prostaglandin synthesis. But the mechanism of its chemopreventive effect on CRC is not clearly understood. Other than CRC, aspirin also showed its potential inhibitory effects on some other types of solid cancer, such as pancreatic, lung, breast and prostate cancers. However, its effects on extragastrointestinal cancer types are still elusive due to lack of reliable supporting evidence from randomized clinical trials. Based on current knowledge, it is unclear why aspirin appears to inhibit CRC more than other cancers. This might be associated with the unique microenvironment comprising trillions of microbes in which CRC resides.