Evaluation of the effect of aspirin and a probiotic on functional dyspepsia

Functional dyspepsia (FD) affects a considerable proportion of Australians and results in significant personal and economic cost. There is as yet no cure for this condition and current treatments are only satisfactory in a subset of patients. New insights into the pathophysiology of FD have found that activation of both mucosal and systemic immune responses are important and have been shown to be linked to symptoms in patients with FD. Specifically, increased mucosal permeability has been linked with mucosal inflammation and our pilot work has shown increased mucosal permeability occurs in FD. In this study we aim to define the effects of pharmacologically induced changes of intestinal permeability on immune activation, upper gut function (sensory & motor function) and symptoms in healthy controls and patients with FD. FD patients and controls will be randomised to receive a nonsteroidal antiinflammtory drug (aspirin) which is known to increase FD symptoms and mucosal permeability or a probiotic (Vivomixx), which is known to reduce the severity of dyspeptic symptoms, and intestinal permeability. In addition recent evidence suggests that that the intestinal microbiome plays a critical role in mucosal inflammation but to date this has not been properly investigated in FD. We aim to define the role of the intestinal microbiome in response to treatment with aspirin and the probiotic Vivomixx using a novel device we have developed and patented that allows targeted aseptic biopsies to be obtained from defined areas of the gastrointestinal mucosa utilising routine endoscopic tests. We will also compare the microbiome in intestinal biopsies from patients with FD and healthy controls to study the link between the diversity of the microbiome and mucosal inflammation. To do this study we will recruit 90 patients with functional dyspepsia and 90 age and sex matched controls without GI symptoms undergoing endoscopy for assessment of iron deficiency with a normal upper endoscopy. They will be randomised to receive either aspirin, Vivomaxx or placebo. They will undergo pre and post treatment testing including fill in questionnaires, donate a blood sample, donate a tissue sample (at baseline only), breath test and a standard nutrient drink challenge. This study will significantly advance the pathophysiology of FD and has the potential to pave the way for future cure of the disease.