Mechanisms underlying the promotion of 5‐hydroxytryptamine secretion in enterochromaffin cells of constipation mice by Bifidobacterium and Lactobacillus

5-Hydroxytryptamine (5-HT) could play a role in alleviating symptoms in constipation. However, the mechanism underlying the role of intestinal flora in the promotion of 5-HT secretion by enterochromaffin cells (ECs) and regulation of the gastrointestinal endocrine system remains unclear.A constipation mouse model was constructed, and the 5-HT, chromogranin A (CGA), substance P (SP), motilin (MTL), dopamine, and noradrenaline expression levels were measured using enzyme-linked immunosorbent assay(Elisa) and immunofluorescence, and key proteins, such as the transient receptor potential (TRP) ion channels/tryptophan hydroxylase (TPH) and olfactory receptor (OR), were determined using western blot. Flow cytometry and in vivo imaging were used to observe microbial colonization in the intestinal tracts of mice.Bifidobacterium animalis F1-7 (F1-7), Lactobacillus paraccasei F34-3 (F34-3), and Lactobacillus plantarum FWDG (FWDG) promoted 5-HT secretion. F1-7 and F34-3 induced CGA expression, increased catecholamine secretion, and activated the CGA/α2A adrenoreceptor (ADRα2A) cascade signal in ECs. FWDG increased noradrenaline levels and activated the ADRα2A signal in ECs. SP content increased in F1-7 and F34-3, and MTL expression increased in FWDG via the above signal. F1-7 and F34-3 downregulated TRPV4 and upregulated TPH, whereas FWDG upregulated OR2A4 for promoting 5-HT secretion by ECs. Finally, we observed that F1-7, F34-3, and FWDG were well colonized in the large intestine.F1-7, F34-3, and FWDG promoted 5-HT secretion in ECs of constipation mice by activating the CGA/ADRα2A cascade signal and regulating the TRP/TPH-OR pathways.