Up regulations of gastric TRPV receptors and decreased serum concentration of BDNF in patients with Functional Dyspepsia

Background:Immune activation has been implicated in the mechanism of post-infectious functional dyspepsia. However, the role of immune activation in FD patients without prior infection remains unclear. Aim:To compare the gastric mucosal and serum expression of brain-derived neurotropic factor (BDNF), transforming growth factor beta (TGFB) families and transient receptor potential vanilloid type (TRPV) families between FD patients and healthy controls. Methods:Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and age-and-sex matched asymptomatic healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous H. pylori infection, psychiatric illness and recent use of NSAID or PPI were excluded. Serum and mucosal biopsies from the gastric corpus were obtained for quantitative assay of mRNA TRPV1, TRPV2, TGFB1 by RT-PCR. Serum concentrations of TGFB families and BDNF were analyzed using immunoassay. The gastric mucosal inflammation was evaluated using Sydney classification. The associations between these assays and dyspeptic symptoms were evaluated. Results:45 [M:F=8:37, mean age: 35.9(9.1)] FD patients were matched with 23 healthy controls [M:F= 8:15, mean age: 36.6(10.2)] respectively. FD patients had PDS as predominant sub-type (PDS: 43, EPS:2). There was no significant difference in the median inflammation score between FD patients and controls (FD: 0 (0-1) Vs Control: 0 (0-1), p=0.54). However, FD patients had significantly higher mRNA expression of gastricTRPV1 (FD: 0.008 ±0.002, Control: 0.003 ±0.001, p=0.03), TRPV2(FD:0.006±0.001, Control: 0.002 ±0.001, p=0.01)and a trend of increased gastric TGFB1 (FD: 0.013 ±0.003, Control:0.005 ±0.002, p=0.07) compared to controls. The serum concentration of BDNF(FD: 240.7 ±11.0, Control: 389.6 ±22.7, p<0.001) were significantly lower in FD patients. Serum TGFB1 and TGFB2 concentrations were significantly correlated with symptoms of belching(R=0.441, p=0.01) and vomiting (R=0.378, R=0.04) in FD patients. Conclusion:Despite the absence of gastric mucosal inflammation, up-regulations of gastric mucosal TRPV1, TRPV2, TGFB1 and down-regulation of serum BDNF were observed in FD patients without prior infection. Gastric mucosal immune activation is associated with symptoms of belching and vomiting, suggesting a causative role of immune activation in the pathogenesis of FD regardless of prior infection status.