Altered Serotonergic Signaling and Immune Activation in the Duodenum Are Not Features of Functional Dyspepsia: Presidential Poster

Introduction: Functional dyspepsia (FD) is a common, disabling condition that is poorly understood. Research has focused mainly on gastric neuromuscular dysfunction but duodenal abnormalities have recently been implicated as important in the pathogenesis of FD. We therefore tested the hypothesis that low-grade inflammation and altered serotonin (5-HT) signaling are features of FD. Methods: Adult subjects who met Rome III criteria for FD, including epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS), were enrolled. Subjects without symptoms of FD but undergoing EGD for other reasons were recruited as controls. During the EGD, 6 mucosal biopsies were taken from the 2nd portion of the duodenum. Tissue was placed immediately into a prepared Eppendorf tube, weighed, and processed for histology, immunohistology, and key features of inflammation and 5-HT signaling, including tryptophan hydroxylase 1 (TpH-1) and serotonin transporter (SERT) RNA, mucosal 5-HT concentrations, and numbers of enterochromaffin (EC) cells. The EPS and PDS groups were compared separately to controls by an unpaired t-test. Results: 14 EPS and 9 PDS subjects were enrolled. 9 controls were also recruited (Dysphagia n=4, Barrett's surveillance n=3, anemia n=2). Inflammation/Immune Activation: No indication of inflammation was seen in FD. The number of eosinophils (Eos) was comparable amongst the three groups as were RNA levels for TNF-α, IL-1β, and IL-10. 5-HT Signaling: Mean total enterochromaffin (EC) cells/total cells did not differ significantly amongst the three groups. The TpH-1 RNA level was significantly lower in EPS than controls (p=0.02), but TpH-1 in the PDS group was comparable to controls. Other values related to 5-HT signaling were comparable amongst the 3 groups. These include SERT RNA levels, numbers of EC cells, and 5-HT content in the mucosal biopsies. Conclusion: There is strong evidence for low-grade inflammation and altered 5-HT signaling in IBS. Our data indicate that this is likely not the case with regard to the duodenal mucosa in FD. No differences in inflammatory markers were detected. Although the TpH-1 RNA level was reduced in the EPS group as compared to controls, other readouts of 5-HT signaling, including EC cell numbers and 5-HT concentration, were not changed. These results suggest that symptoms of FD do not involve inflammatory or serotonergic alterations in the duodenal mucosa. The project was supported by a grant from the ANMS.