Abnormal Barrier Function in Gastrointestinal Disorders

Handb Exp Pharmacol. 2017:239:193-217. doi: 10.1007/164_2016_107.

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.

Keywords: Barrier function; Enteric nervous system; Epithelial integrity; Intestinal permeability; Paracellular transport; Tight junctions; Transport routes.

Publication types

  • Review

MeSH terms

  • Animals
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / physiopathology*
  • Gastrointestinal Diseases / therapy
  • Humans
  • Immunity, Mucosal
  • Intestinal Absorption*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / physiopathology*
  • Permeability
  • Recovery of Function
  • Tight Junctions / metabolism
  • Treatment Outcome