Gastric Inflammation Impacts Serotonin Secretion in a Mouse Model of Helicobacter pylori Vaccination.

Helicobacter pylori infection causes inflammation in the gastric mucosa, and this has been reported to disrupt the gastric microbiota. Serotonin (5-HT) is a key neurotransmitter in the gut-brain axis and plays key roles in intestinal homeostasis and immune function. We investigated gastric serotonin release in H. pylori-infected mice and observed increased release in vaccinated, challenged mice compared to sham vaccinated controls. We investigated the effects of 5-HT on epithelial responses in an in vitro human gastric cancer cell line model (AGS), as well as inflammatory responses and the gastric microbiota in a C57BL/6 mouse model of H. pylori infection. HTR1A was upregulated in the stomachs of mice chronically infected with H. pylori SS1 (3 weeks) compared to uninfected controls, whereas HTR2B was upregulated only in acutely infected mice (3 days), consistent with a role for 5-HT signalling in the development of gastritis. Exposure to 5-HT did not affect NF-κB activation in H. pylori-exposed AGS cells but did inhibit extracellular signal-regulated kinase 1 (ERK1) translocation. Analysis of the gastric microbiota revealed that while vaccination did not significantly affect the diversity of the microbiota, vaccinated animals had increased abundance of Lactobacilli. Our results suggest that local inflammation caused by H. pylori is responsible for increased 5-HT release.