Seroreactivity to Microbial Antigens and Gut‐Homing Immune Responses in Functional Dyspepsia Patients with Postprandial Distress Syndrome

Abstract

Functional dyspepsia (FD) is characterised by recurrent upper gastrointestinal symptoms with no explainable structural changes seen at endoscopy. FD can be classed by two symptom‐based subtypes: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Although FD is associated with an altered microbiome, the nature and consequence of the host‐microbiota interactions and how they relate to FD symptom subtypes is not well understood. We have previously identified an increase in the abundance of Streptococcus spp. in the duodenal microbiota of FD patients compared to controls (Zhong et al. 2017 Gut). We hypothesised that the microbiota of FD patients influenced immune homeostasis and aimed to investigate whether specific species provoked immune responses in patients with FD.New isolates of Streptococcus and Corynebacterium spp. found to be abundant in the duodenal microbiota of FD patients were selected for further analysis. Whole cell lysates from cultures of these bacteria were separated by polyacrylamide gel electrophoresis and transferred to a PVDF membrane for immunoblotting. Immunoblots were probed with plasma from FD patients or non‐FD controls. Density gradient separation was used to isolate peripheral blood mononuclear cells from blood. Cells were then stained with fluorophore conjugated markers for CD3, CD4, integrins α4 & β7 before analysis by flow cytometry to examine changes in proportions of gut‐homing associated lymphocytes (α4+β7+).For lysate isolated from a Streptococcus spp. strain, seroreactive IgG antibody bands were observed at approximately 70kDa in 9 out of 10 FD patients. This band was absent in all but 2 of the control cohort (total n=8). A further band was observed around 30kDa in 9 FD patients (total n=10) that was only present in 3 controls (total n=8). 8 of the 10 patients reported PDS symptoms, of which all demonstrated seroreactivity at 70kDa, and 7 of the total 8 demonstrated a further band at approximately 30kDa. Cross‐reactivity was also observed with a different strain of the same Streptococcus spp. An increase in the proportion of peripheral α4+β7+ T cells (p<0.05) was seen in PDS patients (n=4) but not in EPS (n=3) or EPS/PDS overlap (n=3) patients.Our data suggest an adaptive immune response against duodenal Streptococcus spp. in PDS but not EPS patients. In addition, PDS patients had significantly higher proportions of circulating gut‐homing T cells. These data suggest that PDS is the result of altered microbiota‐immune interactions. With further work, this finding may become a diagnostic indicator of PDS, and provide further insight into the mechanisms that drive FD.Support or Funding InformationNational Health and Medical Research Council Project Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.