Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview

Abstract

Background and Summary: Traditionally, functional gastrointestinal disorders (FGID), including functional dyspepsia or irritable bowel syndrome (IBS), are defined by more or less specific symptoms and the absence of structural or biochemical abnormalities that cause these symptoms. This concept is now considered to be outdated; if appropriate tests are applied, structural or biochemical abnormalities that explain or cause the symptoms may be found in many patients. Another feature of FGID are the highly prevalent psychiatric comorbidities, such as depression and anxiety. It is implied that mood disorders “cause” gastrointestinal symptoms. In fact, epidemiological data now provide strong evidence that in subsets of cases, gastrointestinal (GI) symptoms arise first and mood disorders occur later, while in other patients the reverse appears to happen. Possible mechanisms for gut-brain dysfunction have been identified, with systemic minimal inflammation as a causal factor in at least some subjects. Other mechanisms that play a role in FGID include chronic infections, intestinal microbiota, low-grade mucosal inflammation including the increase of eosinophils, systemic immune activation, altered intestinal permeability, in diarrhea predominant IBS altered bile salt metabolism, abnormalities in the serotonin metabolism and genetic factors. All these factors might be modulated by environmental factors such as diet. Key Messages: While a number of factors can be linked to specific symptoms (e.g., pain or diarrhea), it is evident that the symptom-based categorization of patients will not allow targeted treatments that specifically address the underlying pathophysiology.

Duodenal low‐grade inflammation and expression of tight junction proteins in functional dyspepsia

“…Increased mucosal permeability is one pathogenetic pathway of FGID . Claudins are important as TJ proteins .…”

“…Increased mucosal permeability is one pathogenetic pathway of FGID. [35][36][37] Claudins are important as TJ proteins. 38 Vanheel et al found significantly lower expression of occludin but not of claudin-3 and claudin-4, and expression of ZO-1, beta-catenin, and Ecadherin at junctions was significantly lower in patients with FD.…”

Irritable bowel syndrome, mental health, and quality of life: Data from a population‐based survey in Germany (SHIP‐Trend‐0)

“…Despite increasing knowledge about potential mechanisms such as gut dysfunction, hypersensitivity, changes in membrane permeability, disturbed gut motility, low-grade inflammation, alteration in microbiota, and disturbances in brain-gut axis, many questions about IBS pathophysiology remain open. 10 Some risk factors for the development of IBS are well established: Young age and female sex are demographic risk factors. 9,11 Female predominance in prevalence during the first 60-70 years of life and a dissolution of this gender difference in people aged >65 years suggest an influence of gonadal sex hormones on IBS.…”

“…Despite increasing knowledge about potential mechanisms such as gut dysfunction, hypersensitivity, changes in membrane permeability, disturbed gut motility, low‐grade inflammation, alteration in microbiota, and disturbances in brain‐gut axis, many questions about IBS pathophysiology remain open …”

A Case Study of Familiar Gastrointestinal Pathologies at Risk of Cancer. Early Detection of Degenerative Signals by Oxidative Stress Biomarkers

“…Functional disorders are those in which the gastrointestinal (GI) tract looks normal but doesn't work properly [1]. They are the most common problems affecting the GI tract (including the colon and rectum).…”