Intestinal
melatonin exerts diverse biological effects on the body. Our previous research showed that the abundance of the
butyrate-producing bacteria, Roseburia, is positively related to the expression of colonic mucosal
melatonin. However, the detailed relationship is unclear. Therefore, we aimed to explore whether Roseburia regulates intestinal
melatonin and its underlying mechanisms. Male Sprague-Dawley germfree rats were orally administered with or without Roseburia hominis. R. hominis treatment significantly increased the intestinal
melatonin level. The concentrations of
propionate and
butyrate in the intestinal contents were significantly elevated after gavage of R. hominis.
Propionate or
butyrate treatment increased
melatonin,
5-hydroxytryptamine (5-HT),
arylalkylamine N-acetyltransferase (AANAT), and phosphorylated
cAMP-response element-binding protein (p-CREB) levels. When pretreated with
telotristat ethyl, the inhibitor of
tryptophan hydroxylase (TPH), or
siRNA of Aanat, or 666-15, i.e., an inhibitor of CREB,
propionate, or
butyrate, could not promote
melatonin production in the pheochromocytoma cell line BON-1. Metabolomics analysis showed that
propionate and
butyrate stimulation regulated levels of some metabolites and some metabolic pathways in BON-1 cell supernatants. In conclusion,
propionate and
butyrate, i.e., metabolites of R. hominis, can promote intestinal
melatonin synthesis by increasing
5-HT levels and promoting p-CREB-mediated Aanat transcription, thereby offering a potential target for ameliorating
intestinal diseases.