The majority of peripheral serotonin (5-HT) is produced in the digestive tract and plays a crucial role in controlling intestinal peristalsis and energy metabolism. The serotonin transporter (SERT), expressed in intestinal epithelial cells, regulates the available amount of 5-HT. Recently, a functional CpG site (CpG3) was identified in the SERT gene promoter region, and its expression may be subject to epigenetic regulation. Coffee is the most widely consumed beverage worldwide and exhibits a U- or J-shaped relationship with the risk of a variety of diseases. While caffeine has traditionally been recognized as a key component of coffee, the physiological activity of dietary polyphenols, which can alter DNA methylation patterns, has recently gained attention.
In this study, the impact of habitual excessive coffee consumption on intestinal SERT expression was investigated using the Caco-2 cell line, an intestinal epithelial cell model. The uptake of 5-HT by SERT and its mRNA levels significantly and dose-dependently decreased following exposure to regular coffee and decaffeinated coffee for 24 to 48 hours. On the other hand, exposure to caffeine did not affect SERT mRNA levels. Additionally, well-known compounds of coffee such as chlorogenic acid did not exhibit any effects. Finally, the influence of coffee on the CpG3 methylation state was evaluated using pyrosequencing. Coffee exposure induced hypermethylation at CpG3.
This study reports the potential of excessive coffee consumption to decrease intestinal SERT expression and disrupt peripheral 5-HT regulation.