Serotonin receptors and their association with the immune system in the gastrointestinal tract of weaning piglets

Abstract

Background: Immune cell activation and perpetuation of inflammation have been attributed to the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). Our hypothesis was that the 5-HT system plays a role in GI health and immunity in post-weaning piglets. A disruption of the 5-HT system post-weaning with transcriptional upregulation of 5-HT receptors may be linked to increased cytokine mRNA abundance and immune system activation. Methods: The objective of this exploratory study was to assess the relationship between 5-HT receptor expression and immune system biomarkers in piglets at 1 (n = 9) and 15 (n = 10) days post-weaning. The mRNA transcript abundance of three 5-HT receptors (5-HTR3, 5-HTR4, and 5-HTR7) measured in jejunum and colon tissues were used to determine the relationship with the immune system and jejunal morphometry at 2 timepoints post-weaning using correlations, mixed models, and multivariate analysis techniques. Results: Overall, 5-HT receptor mRNA expression decreased from day 1 to day 15 post-weaning. Time × tissue interactions showed the lowest 5-HTR3 expression in the colon and lower 5-HTR7 expression in the jejunum at 15 days post-weaning. 5-HTR3 and 5-HTR4 expression were negatively associated with pro-inflammatory (IFN-ɣ) and anti-inflammatory (IL-10 and IL-12β) cytokines in jejunum, and with TNF-α in the colon at 1-day post-weaning. At 15 days post-weaning, 5-HTR3 in the colon was negatively associated with pro-inflammatory (IL-1α, IL-1β, TNF-α, IL-8, and IFN-ɣ) and anti-inflammatory (IL-10 and IL-12β) cytokines. Furthermore, 5-HTR7 expressed a predominantly pro-inflammatory profile (IFN-α, IL-1α, IL-1β, IL-8, TNF-α and IL-12α) in the jejunum at the same timepoint, whereas colonic 5-HTR7 expression was negatively correlated with IL-1α, IL-1β, IL-10 and TGF-β. Lastly, positive correlations were found for increased expression of 5-HTR4 receptor with villus height, 5-HTR7 receptor expression and crypt depth, and increased expression of 5-HTR3 and 5-HTR4 receptor with villus height to crypt depth ratio at 1-day post-weaning. Conclusions: The 5-HT receptor mRNA abundance was associated with the immune system and intestinal morphometry in piglets. The 5-HT receptors were highly expressed at weaning in both jejunum and colon tissues relative to 15 days post-weaning. Although a clear relationship between immune system and 5-HTR expression is observed, particularly at day 15, a cause-consequence cannot be proven with current data. Further research is warranted to elucidate the effects of 5-HT on gastrointestinal inflammation during the weaning process in piglets, which could be the basis for new interventions to ease weaning stress.