To explore the mechanism of Mosapride in improving 5-hyd roxytryptamine metabolic pathway, gut bacteria and esophageal inflammation in mice under stress.

8 week old SPF male mice were randomly divided into control, stress and mosapride intervention group (n=6); The mice in the stress and mosapride were restricted in the self-made restraint device for 2h every day and kept for 14 days period; The pathological changes of esophagus were observed by HE staining; tryptophan (TPH), tryptophan hydroxylase-1 (TPH-1), indoleamine 2,3 dioxygenase 1 (IDO-1), tryptophan 2,3 dioxygenase (TDO), canine uric acid (KYN), 5-HT,5-HT4R, F4/80, CD68 and inflammatory factors [interleukin-1 β (IL-1 β), toll-like receptor-4 (TLR-4), tumor necrosis factor-α (TNF-ɑ)] mRNA level were detected by RT-PCR; The 16s rRNA high-throughput sequencing technology was used to detect the intestinal flora of mice.

The mRNA expression levels of 5-HT and 5-HT4R were decreased in the stress group (P<0.001); Mosapride increased the mRNA levels of 5-HT and 5-HT4R (P<0.01). The mRNA level of enzymes (IDO-1, TDO, KYN) in 5-HT metabolic pathway was increased in the stress group (P<0.01, P<0.001); stress reduced the mRNA expression levels of TPH-1 and TPH (P<0.01, P<0.001); Mosapride intervention can improve the abnormal expression of 5-HT metabolic pathway enzymes induced by stress (P<0.01). The microbial diversity of mice in stress group was low; Mosapride intervention significantly improved the abnormal changes of Helicobacterceae, Alloprevotella and Lactobacillus in stress mice. Mosapride significantly inhibited the infiltration of esophageal mucositis induced by stress, and suppressed over expressions of immune cells (CD68, F4/80) and inflammatory factors(IL-1β, TLR-4, TNF-ɑ) (P<0.001).

Mosapride can inhibit the occurrence of abnormal intestinal flora structure and esophageal inflammation induced by stress through regulating 5-HT metabolism.