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Review
. 2020 May 28:10:248.
doi: 10.3389/fcimb.2020.00248. eCollection 2020.

The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders

Madushani Herath  1 , Suzanne Hosie  2 , Joel C Bornstein  1 , Ashley E Franks  3 , Elisa L Hill-Yardin  1   2
Affiliations
Review

The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders

Madushani Herath et al. Front Cell Infect Microbiol. .

Abstract

Mucus is integral to gut health and its properties may be affected in neurological disease. Mucus comprises a hydrated network of polymers including glycosylated mucin proteins. We propose that factors that influence the nervous system may also affect the volume, viscosity, porosity of mucus composition and subsequently, gastrointestinal (GI) microbial populations. The gut has its own intrinsic neuronal network, the enteric nervous system, which extends the length of the GI tract and innervates the mucosal epithelium. The ENS regulates gut function including mucus secretion and renewal. Both dysbiosis and gut dysfunction are commonly reported in several neurological disorders such as Parkinson's and Alzheimer's disease as well in patients with neurodevelopmental disorders including autism. Since some microbes use mucus as a prominent energy source, changes in mucus properties could alter, and even exacerbate, dysbiosis-related gut symptoms in neurological disorders. This review summarizes existing knowledge of the structure and function of the mucus of the GI tract and highlights areas to be addressed in future research to better understand how intestinal homeostasis is impacted in neurological disorders.

Keywords: MUC-2; goblet cells; intestine; microbes; mucus; neurological disorders.

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Figures

Figure 1
Figure 1
The structure of the mucus layer varies with regional locations within the GI tract. (A) The small intestine contains a single layer of mucus, which is loosely attached to the epithelium and easily penetrable. Bacteria within the small intestine are primarily repelled from the epithelium by antibacterial modulators. (B) The distal colon contains two mucus layers; a stratified adherent inner mucus layer and loosely adhesive outer mucus layer. The inner mucus layer of the colon is essentially sterile and the outer mucus layer harbors the intestinal microbiota.
Figure 2
Figure 2
Neuronal innervation of goblet cells in the intestinal mucosa. Neurons of the submucosal plexus (SMP) innervate goblet cells by release of neurotransmitters such as acetylcholine (ACh) and vasoactive internal peptide (VIP). Maturation of goblet cells is influenced by SAM pointed domain-containing Ets transcription factor (Spdef), Wnt/Notch signaling and neuronal activity. Mature goblet cells have a characteristic goblet shape. The apical region is distended by the presence of mucin granules, giving the cell the characteristic cup shape with other cellular organelles condensed in the basal “stem-like” region. Muc-2 protein comprises multiple O-glycans arranged in a “bottle brush” like formation. SMP, submucosal plexus; CM, circular muscle; MP, myenteric plexus; LM, longitudinal muscle; EC cell, enteroendocrine cells.
Figure 3
Figure 3
How neurological disease may impact mucus production. Schematic representation of potential changes in mucus production and microbial communities in neurological disorders. SMP, submucosal plexus; CM, circular muscle; MP, myenteric plexus; LM, longitudinal muscle.
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