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International Journal of Pharmaceutics Oct 2017Mucus is a selective barrier to particles and molecules, preventing penetration to the epithelial surface of mucosal tissues. Significant advances in transmucosal drug... (Review)
Review
Mucus is a selective barrier to particles and molecules, preventing penetration to the epithelial surface of mucosal tissues. Significant advances in transmucosal drug delivery have recently been made and have emphasized that an understanding of the basic structure, viscoelastic properties, and interactions of mucus is of great value in the design of efficient drug delivery systems. Mucins, the primary non-aqueous component of mucus, are polymers carrying a complex and heterogeneous structure with domains that undergo a variety of molecular interactions, such as hydrophilic/hydrophobic, hydrogen bonds and electrostatic interactions. These properties are directly relevant to the numerous mucin-associated diseases, as well as delivering drugs across the mucus barrier. Therefore, in this review we discuss regional differences in mucus composition, mucus physicochemical properties, such as pore size, viscoelasticity, pH, and ionic strength. These factors are also discussed with respect to changes in mucus properties as a function of disease state. Collectively, the review seeks to provide a state of the art roadmap for researchers who must contend with this critical barrier to drug delivery.
Topics: Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Mucins; Mucus; Viscosity
PubMed: 28917986
DOI: 10.1016/j.ijpharm.2017.09.018 -
Frontiers in Cellular and Infection... 2012Mucus colonization is an essential early step toward establishing successful infection and disease by mucosal pathogens. There is an emerging literature implicating... (Review)
Review
Mucus colonization is an essential early step toward establishing successful infection and disease by mucosal pathogens. There is an emerging literature implicating specific mucin sub-types and mucin modifications in protecting the host from Campylobacter jejuni infection. However, mucosal pathogens have evolved sophisticated mechanisms to breach the mucus layer and C. jejuni in particular appears to harbor specific adaptations to better colonize intestinal mucus. For example, components of mucus are chemotactic for C. jejuni and the rheological properties of mucus promote motility of the organism. Furthermore, recent studies demonstrate that mucins modulate the pathogenicity of C. jejuni in a species-specific manner and likely help determine whether these bacteria become pathogenic (as in humans), or adopt a commensal mode of existence (as in chickens and other animals). This review focuses on recent advances in understanding the complex interplay between C. jejuni and components of the mucus layer.
Topics: Animals; Campylobacter jejuni; Host-Pathogen Interactions; Humans; Intestinal Mucosa; Mucus
PubMed: 22919607
DOI: 10.3389/fcimb.2012.00015 -
ACS Synthetic Biology Feb 2020Mucus in the gastrointestinal (GI) tract is the primary point-of-interaction between humans and their gut microbiota. This intimates that mucus not only ensures...
Mucus in the gastrointestinal (GI) tract is the primary point-of-interaction between humans and their gut microbiota. This intimates that mucus not only ensures protection against endogenous and exogenous opportunists but also provisions for the human microbiota to reside and flourish. With the emergence of living therapeutics, engineered microbes can deliver and produce increasingly complex medicine, and controlling the mucoadhesive properties of different microbial chassis can dictate dose-response in a patient. Here we present a redesigned, , plate-based assay to measure the mucus adhesion of various probiotics. Cell-mucus interactions were isolated by immobilizing mucus to the plate surface. Binding parameters were derived for each probiotic strain by measuring cell adhesion over a wide range of cell concentrations, providing dose-dependent adhesion metrics. Surface proteins and cell components known to influence mucoadhesion were then heterologously expressed or altered in MG1363 and Nissle 1917 to control mucus-binding capacity, avidity, and cooperativity.
Topics: Animals; Bacterial Adhesion; Escherichia coli; Fluoresceins; Humans; Lactococcus lactis; Microscopy, Fluorescence; Mucin-2; Mucus; Probiotics; Swine
PubMed: 31909976
DOI: 10.1021/acssynbio.9b00356 -
American Journal of Physiology. Lung... Oct 2019
Topics: Intubation, Intratracheal; Mucus; Respiratory System; Rheology
PubMed: 31508979
DOI: 10.1152/ajplung.00362.2019 -
Trends in Microbiology Nov 2021Efficient penetration of the mucus layer is needed for respiratory viruses to avoid mucociliary clearance prior to infection. Many respiratory viruses bind to glycans on... (Review)
Review
Efficient penetration of the mucus layer is needed for respiratory viruses to avoid mucociliary clearance prior to infection. Many respiratory viruses bind to glycans on the heavily glycosylated mucins that give mucus its gel-like characteristics. Influenza viruses, some paramyxoviruses, and coronaviruses avoid becoming trapped in the mucus by releasing themselves by means of their envelope-embedded enzymes that destroy glycan receptors. For efficient infection, receptor binding and destruction need to be in balance with the host receptor repertoire. Establishment in a novel host species requires resetting of the balance to adapt to the different glycan repertoire encountered. Growing understanding of species-specific mucosal glycosylation patterns and the dynamic interaction with respiratory viruses identifies the mucus layer as a major host-range determinant and barrier for zoonotic transfer.
Topics: Glycosylation; Host Specificity; Mucins; Mucus; Polysaccharides; Viruses
PubMed: 33875348
DOI: 10.1016/j.tim.2021.03.014 -
Human Vaccines & Immunotherapeutics Apr 2022In addition to the classical immunological functions such as neutralization, antibody-dependent cellular cytotoxicity, and complement activation, IgG antibodies possess... (Review)
Review
In addition to the classical immunological functions such as neutralization, antibody-dependent cellular cytotoxicity, and complement activation, IgG antibodies possess a little-recognized and under-utilized effector function at mucosal surfaces: trapping pathogens in mucus. IgG can potently immobilize pathogens that otherwise readily diffuse or actively swim through mucus by forming multiple low-affinity bonds between the array of pathogen-bound antibodies and the mucin mesh. Trapping in mucus can exclude pathogens from contacting target cells, and facilitate their rapid elimination by natural mucus clearance mechanisms. Despite the fact that most infections are transmitted at mucosal surfaces, this muco-trapping effector function has only been revealed within the past decade, with the evidence to date suggesting that it is a universal effector function of IgG-Fc capable of immobilizing both viral and highly motile bacterial pathogens in all major mucosal secretions. This review provides an overview of the current evidence for Fc-mucin crosslinking as an effector function for antibodies in mucus, the mechanism by which the accumulation of weak Fc-mucin bonds by IgG bound to the surface of a pathogen can result in immobilization of antibody-pathogen complexes, and how trapping in mucus can contribute to protection against foreign pathogens.
Topics: Antibody-Dependent Cell Cytotoxicity; Immunoglobulin G; Mucins; Mucus
PubMed: 34314289
DOI: 10.1080/21645515.2021.1939605 -
Cold Spring Harbor Perspectives in... Aug 2013In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic... (Review)
Review
In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic inflammation and bacterial infections. Physiotherapy using a variety of airway clearance techniques (ACTs) represents a key treatment regime by helping clear the airways of thickened, adhered, mucus and, thus, reducing the impact of lung infections and improving lung function. This article aims to bridge the gap between our understanding of the physiological effects of mechanical stresses elicited by ACTs on airway epithelia and the reported effectiveness of ACTs in CF patients. In the first part of this review, the effects of mechanical stress on airway epithelia are discussed in relation to changes in ion transport and stimulation in airway surface layer hydration. The second half is devoted to detailing the most commonly used ACTs to stimulate the removal of mucus from the airways of patients with CF.
Topics: Bronchi; Cystic Fibrosis; Humans; Ion Transport; Lung; Mucus; Physical Therapy Modalities; Respiratory Mucosa; Treatment Outcome
PubMed: 23751214
DOI: 10.1101/cshperspect.a009720 -
The European Respiratory Journal Jun 1999Cough and expectoration of mucus are the best-known symptoms in patients with pulmonary disease. The most applied intervention for these symptoms is the use of chest... (Review)
Review
Cough and expectoration of mucus are the best-known symptoms in patients with pulmonary disease. The most applied intervention for these symptoms is the use of chest physiotherapy to increase bronchial mucus transport and reduce retention of mucus in the airways. Chest physiotherapy interventions can be evaluated using different outcome variables, such as bronchial mucus transport measurement, measurement of the amount of expectorated mucus, pulmonary function, medication use, frequency of exacerbation and quality of life. Measurement of the transport rate of mucus in the airways using a radioactive tracer appears to be an appropriate outcome variable for short-term studies. Evaluation of chest physiotherapy only with pulmonary function tests appears to be inadequate in short-term studies. The popularity of using pulmonary function tests is probably based more on the availability of the instruments than on a theoretical basis related to the question of chest physiotherapy improving mucus transport. Quality of life and progression of the disease are not often used as outcome variables, but it may be worthwhile to use these in the future.
Topics: Bronchi; Humans; Mucociliary Clearance; Mucus; Physical Therapy Modalities; Respiratory Therapy; Respiratory Tract Diseases
PubMed: 10445628
DOI: 10.1183/09031936.99.13614879 -
European Journal of Pharmaceutics and... Apr 2022Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from...
Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from the epithelium. Our aim was to characterize the composition and structure of mucus throughout the various GI segments in dog. Mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum), and large intestine (cecum, proximal and distal colon) from dogs. Composition was determined by multi-omics. Structural properties were investigated using cryoSEM and rheology. GI mucus contained 74-95% water and maintained a pH around 6.5. The proteome was similar across the different GI segments. The highest abundant secreted gel-forming mucin in the gastric mucus was mucin 5AC, whether mucin 2 had highest abundance in the intestinal mucus. Lipid and metabolite abundance was generally higher in the jejunal mucus than the colonic mucus. CryoSEM microscopy revealed smaller pore size in small intestinal mucus, which increased in the large intestine. All mucus samples showed shear-thinning behavior and characteristics of gel-like structure. In conclusion, the mucus is a highly viscous and hydrated material. These data provide an important baseline for future studies on human and canine intestinal diseases and the dog model in drug absorption.
Topics: Animals; Colon; Dogs; Gastrointestinal Tract; Intestinal Mucosa; Intestine, Small; Mucus; Stomach
PubMed: 35227857
DOI: 10.1016/j.ejpb.2022.02.019 -
Trends in Molecular Medicine Jan 2022The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a... (Review)
Review
The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a site for allergic sensitization to food. In this context, we focus on an important but overlooked part of the mucosal barrier in pathogenesis, the glycoprotein-rich mucus layer, and call attention to both beneficial and detrimental aspects of mucus-gut microbiome interactions. Studying the intricate links between the mucus barrier, the associated bacteria, and the mucosal immune system may advance our understanding of the mechanisms and inform prevention and treatment strategies in food allergy.
Topics: Bacteria; Food Hypersensitivity; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mucus
PubMed: 34810087
DOI: 10.1016/j.molmed.2021.10.004