Microbial dysbiosis alters serotonin signaling in a post-inflammatory murine model of visceral pain

Serotonin (5-HT) is a multifunctional signaling molecule in the gastrointestinal (GI) tract. 5-HT synthesis is regulated by the gut microbiota. Microbial dysbiosis has been implicated in visceral pain and persistent alterations in gut function that occur following inflammation. Here we tested the hypothesis that alterations in gut microbiota in a post-inflammatory model of visceral pain contribute to dysregulated 5-HT signaling. We used mice treated with dextran sodium sulfate (DSS) 42 days earlier (post-colitis) or untreated mice as donors for fecal microbiota transplants (FMTs) into germ-free mice to explore changes in enterochromaffin (EC) cell populations, expression of 5-HT synthesis, transport, and degradation genes, levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT release. Significant differences were observed in EC cells, Tph1, Slc6a4, and Maoa gene expression, 5-HT and 5-HIAA levels and 5-HT release between germ-free mice and mice receiving an FMT from either control or post-colitis donor mice. We observed no differences in the total number of EC cells, Tph1, or Slc6a4 gene expression of mice after FMT from post-colitis or control mice. However, there was a significant increase in Maoa gene expression in the terminal ileum, an increased 5-HIAA/5-HT ratio in the proximal colon and reduced 5-HT release to mechanical and chemical stimulation in the proximal and distal colon after FMT from post-colitis mice. Collectively, these findings provide additional evidence that the gut microbiota regulates 5-HT signaling. Moreover, they reveal functional changes in EC cell sensitivity in the presence of an altered microbiota after recovery from inflammation.