The Intake of Coffee Increases the Absorption of Aspirin in Mice by Modifying Gut Microbiome

Abstract

The absorption of orally administered aspirin into the blood was affected by gastrointestinal environmental factors such as gut pH, digestive enzymes, and microbiota. The intake of coffee affects the pharmacological effects of aspirin. Therefore, we examined the gut microbiota-mediated effect of coffee bean extract (CBE) intake on the pharmacokinetics of aspirin in mice. The intake of CBE modified the gut microbiota composition and their alpha- and beta-diversities: It decreased the Proteobacteria, Helicobacteriaceae, and Bacteroidaceae populations in the fecal microbiota composition, while the S24-7_f (Muribaculaceae) and Lactobacillaceae populations increased. The fecal aspirin-hydrolyzing activities of humans and mice to salicylic acid were 0.045 +/- 0.036 mu mole/h/g and 0.032 +/- 0.003 mu mole/h/g, respectively. However, CBE treatment significantly suppressed the aspirin-hydrolyzing activity in mice. Furthermore, the area under the serum concentration-time curves (AUCs) of aspirin and salicylic acid were 0.265 +/- 0.050 mu g center dot h/mL and 16.224 +/- 5.578 mu g center dot h/mL in CBE-treated mice, respectively, and 0.248 +/- 0.042 mu g center dot h/mL and 10.756 +/- 2.071 mu g center dot h/mL in control mice, respectively. Moreover, CBE treatment suppressed the multidrug resistance protein 4 (Mrp4) expression in the intestines of mice, while the P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) expression was not affected. Furthermore, the CBE-treated mouse fecal lysate suppressed Mrp4 expression in Caco-2 cells compared to that of vehicle-treated mice, while CBE treatment did not affect Mrp4 expression. Oral gavage of caffeine also suppressed the Mrp4 expression in the intestines of mice. These findings suggest that intake of coffee can increase the absorption of aspirin by modifying the gut microbiome.