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.