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

<i>Helicobacter pylori</i> 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 <i>H. pylori</i>-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 <i>H. pylori</i> infection. HTR1A was upregulated in the stomachs of mice chronically infected with <i>H. pylori</i> 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 <i>H. pylori</i>-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 <i>Lactobacilli</i>. Our results suggest that local inflammation caused by <i>H. pylori</i> is responsible for increased 5-HT release.