The Effect of a Low FODMAP Diet in Functional Dyspepsia Patients With Meal Related Symptoms on Complaint Pattern and Urinary Histamine Excretion

Functional dyspepsia Functional dyspepsia (FD) is defined as "symptoms affecting daily life which are thought to originate from the gastroduodenal region, such as postprandial fullness, early satiation, epigastric pain and burning, without underlying organic disease likely to explain the symptoms". FD is very common, with estimates of 10% to 30% prevalence in the general population, and is associated with substantial medical care costs and a considerable health economic impact. A proportion of 20%-25% of the patients with severe and refractory GI symptoms also have psychosocial co-morbidities such as anxiety, depression or somatization and severely impaired daily functioning (about 10% of these patients have work disability). This subgroup is often referred to advanced care, which may be associated with even higher health economic costs.

The pathophysiology of FD remains poorly understood and is most likely heterogeneous. The majority of FD patients have meal-related symptoms (early satiation, postprandial fullness, or epigastric pain or burning or nausea occurring or worsening after a meal). These are referred to as having Postprandial Distress Syndrome (PDS) according to the Rome IV consensus.

Leaky duodenal mucosa Duodenal and small intestinal perturbations seem to play an important role in the generation of dyspeptic symptoms. Through neuro-humoral feedback mechanisms, the duodenum plays a major role in controlling gastric functions. Mechanistic studies support the hypothesis that altered duodenal content or altered duodenal mucosal integrity are present in FD and may trigger impaired nutrient tolerance and impaired accommodation. Closely associated are signs of low grade inflammation with increased numbers of mast cells and eosinophils in the duodenal mucosa, which has been associated to symptoms of postprandial fullness and early satiation. While acute stress can increase intestinal permeability, changes in luminal factors are key candidate mechanisms to explain both mucosal permeability and immune inflammation. Duodenal acid exposure is increased in FD patients and may lead to loss of mucosal integrity and mast cell activation.

Dietary triggers The use of dietary therapeutic approaches such as the FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols) diet to manage gastrointestinal symptoms has been frequently described and controlled studies have showed significant favorable on irritable bowel syndrome (IBS) symptoms such as abdominal pain, bloating and flatulence and it has been shown to be associated to changes in fecal microbiota. A recent study from our group showed that fructans and fructose (two of the FODMAPs) interfere with the normal meal-induced drop in intragastric pressure (IGP) and induce early postprandial occurrence of gastrointestinal symptoms, reminiscent of what happens in FD.

Measuring urinary histamine excretion McIntosh et al made an effort to identify pathophysiological mechanisms by which FODMAPs could cause gastrointestinal symptoms. They studied 20 IBS patients on a high FODMAP diet and 20 IBS patients on a low FODMAP diet. Urine samples were tested using Mass Spectrometry Analysis for metabolites that could potentially be linked to FODMAP induced post prandial distress. Patients on a low FODMAP diet had lower urinary histamine levels than IBS patients on a high FODMAP diet. The investigators hypothesize that urinary histamine excretion could be a surrogate marker for duodenal mastcell activation in patients with FD like described previously. The investigators will also measure the urinary N-methyl histamine excretion which is a more stable metabolite than histamine itself.