The Role of Leaky Gut in Functional Dyspepsia

Abstract

Patients with functional dyspepsia (FD) complain of epigastric symptoms with no identifiable cause. Increased intestinal permeability has been described in these patients, especially in the proximal small bowel or duodenum, and was associated with mucosal immune activation and symptoms. In this review, we discuss duodenal barrier function, including techniques currently applied in FD research. We summarize the available data on duodenal permeability in FD and factors associated to increased permeability, including mucosal eosinophils, mast cells, luminal and systemic factors. While the increased influx of antigens into the duodenal mucosa could result in local immune activation, clinical evidence for a causal role of permeability is lacking in the absence of specific barrier-protective treatments. As both existing and novel treatments, including proton pump inhibitors (PPI) and pre- or probiotics may impact duodenal barrier function, it is important to recognize and study these alterations to improve the knowledge and management of FD.

Endoscopic laser endomicroscopy and “leaky gut” in patients with functional gastrointestinal symptoms and food intolerance

“…Low-grade inflammation exists in the duodenum of patients with FD [4,5,6,7,8,9] and IBS [11]. The trigger for this inflammatory response is unknown but could also be mediated by luminal factors such as food, acid, bile acids, and microbiota [15,16,17]. In our study, patients received a standardized diet bevor eCLE and had no evidence of sugar intolerance or SIBO making luminal factors as the reason for the spontaneous fluorescein leakage unlikely.…”

Understanding neuroimmune interactions in disorders of gut–brain interaction: from functional to immune-mediated disorders

“…Positive associations with altered stool pattern and pain were identified in the majority of the studies, although an inverse association has been reported as well 89. Similarly, multiple studies have reported increased duodenal permeability in FD using in vivo techniques (urinary sugar excretion tests, mucosal impedance and confocal laser endomicroscopy (CLE)) and biopsies in Ussing chambers, although a link with symptom severity was absent in most studies 87…”

“…89 Similarly, multiple studies have reported increased duodenal permeability in FD using in vivo techniques (urinary sugar excretion tests, mucosal impedance and confocal laser endomicroscopy (CLE)) and biopsies in Ussing chambers, although a link with symptom severity was absent in most studies. 87 The expression of several tight junction related proteins, which are the key determinants of epithelial barrier function, in different regions of the GI tract was shown to be altered in IBS and FD, although the reported changes were not consistent between studies. 87 88 Colonic infusion of faecal supernatant of patients with IBS in mice or application of biopsy supernatant on cell lines resulted in lower barrier function, indicating the involvement of luminal mediators.…”

“…However, measurement of intestinal barrier function is complex and contributes to the variability of the reported data. Direct measurement of permeability of endoscopic biopsies in Ussing chambers is still the gold standard, but less frequently used 86 87…”

Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis

“…CRH activates mast cells and induces intestinal epithelial barrier dysfunction [ 12 ]. The increased influx of allergens into the mucosa can result in local immune activation [ 13 ]. Patients with EoE present impaired esophageal epithelial barrier function and increased uptake of allergens [ 14 ].…”