Correlated gene expression encoding serotonin (5‐HT) receptor 4 and 5‐HT transporter in proximal colonic segments of mice across different colonization states and sexes

Abstract

The production and handling of serotonin (5-HT) is an important determinant of colonic motility and has been reported to be altered in gastrointestinal (GI) disorders such as irritable bowel syndrome (IBS). Recent studies suggest that the intestinal microbiota and sex of the host can influence expression of genes involved in 5-HT biosynthesis and signaling. While expression of genes in serotonergic pathways has been shown to be variable, it is unclear whether genes within this pathway are co-regulated. As a first step in that direction, we investigated potential correlations in relative mRNA expression of serotonergic genes, in the proximal colon isolated from male and female mice in different states of microbial association: germ-free (GF), humanized (ex-germ-free colonized with human gut microbiota, HM), and conventionally raised (CR) mice. Among the ten pairwise comparisons conducted between five serotonergic transcripts, Tph1, Chga, Maoa, Slc6a4 and Htr4, we found a strong, positive correlation between colonic expression of Slc6a4 and Htr4 across different colonization states and sexes. We also identified a positive correlation between the expression of Tph1 and Chga; however, there were no correlations observed between any other tested pair of 5-HT-related transcripts. These data suggest that correlated expression of Slc6a4 and Htr4 likely involves co-regulation of genes located on different chromosomes which modulate serotonergic activity in the gut. Further work will need to be done to understand the pathways and cell types responsible for this correlated expression, given the important role of 5-HT in gastrointestinal physiology.

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

“…CGA is an acidic protein molecule, and as a member of the neuropeptide family, it affects gastrointestinal neuroendocrine cells, including ECs. 4 As a precursor peptide, CGA can be broken down into different segments of different tissues and participates in maintaining the stability of the endocrine environment of the body. 22 Compared with the loperamide hydrochloride treatment group, the other groups showed different CGA expression levels (Figure 2); therefore, probiotics could help restore the secretion disorder of CGA in the constipation mouse model.…”

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

“…It is a serotonin-selective transport protein that transports the neurotransmitter 5-HT from synaptic spaces into presynaptic neurons and removes 5-HT from the interstitial space. 34 5-HT is synthesized in enterochromaffin cells and modulates visceral sensitivity of the GI tract. It was reported that SERT could uptake 5-HT into enterocytes to ensure the recapture of serotonin.…”

Relationships Between Distention-, Butyrate- and Pellet-Induced Stimulation of Peristalsis in the Mouse Colon

“…Thus, it may be that butyrate does not have a significant role under normal physiological conditions, but its role might increase under conditions of low activity such as poor fiber intake where mechanical stimulation in the lumen is low. This butyrate action may occur by stimulating 5-HT production in enteroendocrine cells, which may act primarily on 5-HT 4 receptors on sensory nerves (Hoffman et al, 2012;Yu et al, 2015;Reigstad et al, 2016).…”