Abnormal Barrier Function in Gastrointestinal Disorders

Abstract

There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.

Intestinal Permeability, Inflammation and the Role of Nutrients

“…sIgA blocks epithelial-specific receptors on pathogens to prevent their attachment to epithelial cells [25]. Cellular immunity, also called immune barrier, comprises a variety of immune cells that reside in the lamina propria and in Peyer's patches, both of which underlie the intestinal epithelium [26].…”

Functional dyspepsia: from pathogenesis to therapeutic aspects

“…Выявлена значительная связь между степенью повышения проницаемости, уровнем экспрессии адгезивных белков и выраженностью субклинического воспаления. Подтверждением этому являются исследования, в которых сообщается об увеличении количества тучных клеток и эозинофилов в биоптатах слизистой оболочки двенадцатиперстной кишки, что подчеркивает потенциальную роль воспалительных механизмов в патогенезе ФД [29]. Так, в недавнем метаанализе, обобщившем результаты 37 исследований, было продемонстрировано, что у пациентов с ФД по сравнению с группой контроля отмечается увеличение количества тучных клеток (стандартизованная разность средних (СРС) = 0,66, 95% ДИ 0,20-1,13, p = 0,005) и эозинофилов (СРС = 0,95, 95% ДИ 0,66-1,24; p < 0,001) в слизистой оболочке двенадцатиперстной кишки [30].…”

Role of the Duodenum in the Pathogenesis of Functional Dyspepsia: A Paradigm Shift

“…The tight junction is constituted by surface-membrane proteins, including occludin, claudins, junctional adhesion molecules and tricellulin, and intracellular proteins, zonula occludins (ZO)-1, 2, 3, which anchor to the actin cytoskeleton. 70 Adherence junctions are mainly made up of e-cadherin, catenin, and actin filaments. 71,72 In the colonic mucosa of IBS patients, increased permeability has been linked to the down-regulation of ZO-1 and proteasome-mediated occludin degradation 73,74 and mast cell activation was associated with down-regulation and redistribution of ZO-1 and occludin in the jejunum.…”