The intestinal mucosal barrier is composed of epithelial cells that are protected by an overlying host-secreted mucous layer and functions as the first line of defence against pathogenic and non-pathogenic microorganisms. Some microorganisms have evolved strategies to either survive in the mucosal barrier or circumvent it to establish infection. In this Review, we discuss the current state of knowledge of the complex interactions of commensal microorganisms with the intestinal mucosal barrier, and we discuss strategies used by pathogenic microorganisms to establish infection by either exploiting different epithelial cell lineages or disrupting the mucous layer, as well as the role of defects in mucus production in chronic disease.
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Work in the authors’ laboratories was supported by National Institutes of Health R01 and R21 (GM099513 and AI128120) awards (to E.C.M.) and an Innovator Award from the Kenneth Rainin Foundation. Work in their laboratories was also supported by the following grants (to M.S.D.): Luxembourg National Research Fund (FNR) CORE (C15/BM/10318186); FNR AFR Bilateral (11228353); Luxembourg Ministry of Higher Education and Research support (DM-Muc); and Personalized Medicine Consortium of Luxembourg Pump Prime (Die-IBD).
The authors declare no competing interests.
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Refers to symbiotic microorganisms that do not seem to harm (pathogens) or benefit (mutualists) their host. Commensal is arguably an imprecise term to apply to a microorganism, especially considering that any microorganism may display behaviours that are both beneficial and detrimental.
A community of microorganisms, such as the taxonomically diverse and densely populated assemblage of species that inhabits the human gut.
- Inflammatory bowel disease
(IBD). A group of chronic diseases characterized by episodes of relapsing and remitting inflammation. Crohn’s disease and ulcerative colitis are the most common types of IBDs and are thought to develop from a combination of host genetic predisposition, including defects in the gut mucosal and immunological barriers, and environmental factors, such as diet and the microbiota.
- Tight junctions
Multi-protein complexes that form near the apical ends of intestinal epithelial cells, providing tight, water-impermeable and ion-impermeable seals between cells. Proteins that are included in tight junctions include claudins and occludins, which span the membrane and are anchored together outside the cell and are connected to the intracellular cytoskeleton.
- Mucous layer
Mucus, composed mostly of secreted mucin glycoproteins and other substances, is secreted by goblet cells and overlies the intestinal epithelium, forming an adherent and insoluble inner layer and a looser outer layer in the colon.
- Tuft cells
Taste-chemosensory cells that are present in the intestinal epithelium and have an important role in initiating a type 2 immune response to clear parasitic infection. They have a unique appearance that includes a tubulovesicular system and an apical bundle of microfilaments that are attached to a tuft of long, lumen-facing microvilli.
Class of proteins comprising oligosaccharide chains connected to a backbone polypeptide, sometimes thousands of amino acids long, which is modified with glycans in the endoplasmic reticulum. Mucins and other glycoproteins contain O-linked and N-linked glycans attached to serine or threonine and asparagine, respectively.
- Secretory IgA
Immunoglobulin A (IgA) is the most abundant antibody isotype in the human body and occurs in two subtypes: IgA1 and IgA2, which are distinguished by their heavy chains. IgA1 is predominant in the serum, and IgA2 is most abundant in the intestinal tract to bind pathogens by reducing mobility and decreasing proliferation.
- Carbohydrate-active enzymes
(CAZymes). This term encompasses several different groups of enzymes: glycoside hydrolases, polysaccharide lyases, carbohydrate esterases and glycosyltransferases. These groups, and hundreds of more specific enzyme families that they collectively contain, are involved in building and degrading polysaccharides and glycans.
Dietary supplements (most often oligosaccharide or polysaccharide fibres) that selectively increase certain taxonomic groups in the gut microbiota and also exert a positive impact on host health.
- Hidden Markov models
A statistical approach that is often used in bioinformatics to identify hidden, but meaningful, amino acid sequence signals in proteins and can be used to group them into families with similar function.
(IL-22). A cytokine that is part of the IL-10 cytokine family that is produced by activated natural killer and T cells and, in the gut, is responsible for activating epithelial cell regeneration, mucin production and antimicrobial peptide secretion.
- Innate lymphoid cells
(ILCs). A group of innate immune cells that are characterized by the absence of antigen-specific B or T cell receptors.
- Colonization resistance
A phenomenon by which the presence of a healthy microbiota inhibits invasion by external pathogens. In the gut, this state has been ascribed to the inhibition of many enteric pathogens, which are more adept at gaining an infection foothold after a major perturbation, such as antibiotic treatment.
A broad family of plant, animal and bacterial proteins defined by their ability to bind to certain carbohydrates with moderate to high affinity.
- Type III secretion systems
(T3SSs). Needle-like complexes related to the bacterial flagellum that are an important virulence factor of Gram-negative bacteria. They enable pathogenic bacteria to inject effector proteins into the cytoplasm of the host target cell and modify a variety of cellular responses.
- Molecular chaperone
Type of protein that assists in the folding and unfolding of other proteins. They prevent aggregation by binding to non-native structures and therefore support the folding process.
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Martens, E.C., Neumann, M. & Desai, M.S. Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier. Nat Rev Microbiol 16, 457–470 (2018). https://doi.org/10.1038/s41579-018-0036-x
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