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Short chain fatty acids contribute to gut microbiota-induced promotion of colonic melatonin receptor expression.

Melatonin plays an important role in various gut functions through melatonin receptors. The gut
microbiota/gut hormone axis has recently received increasing attention. However, the relationship between
the gut microbiota and melatonin receptors has not yet been evaluated. We aimed to determine the effect of
the gut microbiota on colonic melatonin receptor expression in germ-free (GF) rats and to further explore
the potential mechanism in Caco-2 cells. In this study, GF rats were transplanted with fecal samples from
a healthy human donor. Subsequently, 16S rRNA sequencing was performed to analyze the microbial
communities. Colon tissue was collected for immunohistochemical analysis. The correlations between
melatonin receptor expression and the gut microbiota were assessed. Melatonin receptor expression in
Caco-2 cells was detected by Western blot. We found that fecal microbiota transplantation significantly
increased the expression of colonic melatonin receptors in GF rats. The amount of fecal Short chain
fatty acids (SCFAs) was significantly higher in fecal microbiota transplantation (FMT) rats than in GF
rats. SCFA-producing bacteria, such as Alistipes and Blautia, were positively correlated with colonic
melatonin receptor expression in FMT rats. Additionally, acetate and propionate significantly increased
melatonin receptor-1 expression in Caco-2 cells. Therefore, the gut microbiota may promote melatonin
receptor expression, and the mechanism may involve the action of SCFAs. This finding may facilitate the
development of new therapeutic treatments for various gastrointestinal disorders.