Influence of Aspirin on Human Gut Microbiota Composition and Metabolome

The Influence of Aspirin on Human Gut Microbiota Composition and Metabolome: Contributing to the Therapeutic Effects of the Drug

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.

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.

It is commonly accepted that aspirin exerts its chemopreventive effects by inhibiting catalytic enzymes cyclooxygenase (COX) -1 and COX-2 involved in prostaglandin synthesis.This hypothetic mechanism is supported by clinical data from two large cohorts that found that the regular use of aspirin reduced the risk of CRC with high expression of COX-2 but not with low or no expression of COX-2.

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. Therefore, the investigator hypothesizes that there is a link between the chemopreventive mechanism of aspirin, gut microbiota as well as the metabolome.

During the past decade, evidence has accumulated that microbiota in the host is highly sensitive to the gut microenvironment since its composition and activity can be rapidly and reproducibly changed by diet or nutrients. As such, an acidic drug like aspirin may be able to alter the gut microbiota composition. It is thus conceivable that the CRC preventive action of aspirin may be through the alteration of host gut microbes.

Inclusion Criteria:

• NSAID naïve during the last month;
• absence of drugs, nutrient supplements, probiotics, prebiotics and synbiotics that might interfere with microbial homeostasis for all participants;
• no past history of gastrointestinal bleeding or ulcers;
• absence of historical aspirin-induced side effects;
• voluntary and willing to cooperate during treatment; and
• consent with treatment and sample collection schedule

Exclusion Criteria:

• unfit symptoms, such as epigastric pain, acid reflux, eructation and dyspepsia;
• diagnosis of any disease during the past 3 months;
• diarrhea within the previous 7 days;
• history of alcohol abuse, defined as >80 g/d in men and >40 g/d in women;
• pregnancy; and
• mental illness rendering the participants unable to understand the nature, scope, and possible consequences of the study