Mucus, Microbiomes and Pulmonary Disease

Abstract

The respiratory tract harbors a stable and diverse microbial population within an extracellular mucus layer. Mucus provides a formidable defense against infection and maintaining healthy mucus is essential to normal pulmonary physiology, promoting immune tolerance and facilitating a healthy, commensal lung microbiome that can be altered in association with chronic respiratory disease. How one maintains a specialized (healthy) microbiome that resists significant fluctuation remains unknown, although smoking, diet, antimicrobial therapy, and infection have all been observed to influence microbial lung homeostasis. In this review, we outline the specific role of polymerizing mucin, a key functional component of the mucus layer that changes during pulmonary disease. We discuss strategies by which mucin feed and spatial orientation directly influence microbial behavior and highlight how a compromised mucus layer gives rise to inflammation and microbial dysbiosis. This emerging field of respiratory research provides fresh opportunities to examine mucus, and its function as predictors of infection risk or disease progression and severity across a range of chronic pulmonary disease states and consider new perspectives in the development of mucolytic treatments.

Cystic Fibrosis Mucus Model to Design More Efficient Drug Therapies

“…Although mucus production is needed to avoid environmental threats, either overproduction or a dysfunctional clearance of mucus is a hallmark of all mucus-related pathologies such as cystic fibrosis (CF). In these disorders, an overexpression of mucins, accumulation of extracellular DNA as well as cellular debris, and the persistent presence of bacteria confer mucus stasis, leading to a vicious cycle of infection and inflammation that can be chronically sustained. , Moreover, the lack of function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein leads to a dehydrated form of mucus, which is characterized by a reduced mesh size (60–300 nm) in comparison to physiological mucus (497–503 nm) . As a result, in CF and bronchiectasis, daily sputum production is a crucial marker for physicians to evaluate disease severity and treatment response …”

Untangling Mucosal Drug Delivery: Engineering, Designing, and Testing Nanoparticles to Overcome the Mucus Barrier

“…The lungs boast a large surface area, high vascularization, thin epithelial barrier, and 10- to 200-fold greater relative therapeutic bioavailability compared to other noninvasive delivery schemes . The conditions are generally less harsh, where the main limitations are the mucus barrier coating the airways (excluding the gas exchanging surfaces of the deep lung) and the mucociliary clearance effect as well as the action of pulmonary macrophages. , Since the delivery of nanomedicines via the pulmonary route must be achieved through inhalation rather than ingestion, it poses a unique challenge in designing the drug delivery vehicle. For example, the size distribution of aerosolized nanoparticulate and microparticulate systems influences the region of the respiratory tract where the drug delivery system is deposited.…”

Methods of Sputum and Mucus Assessment for Muco-Obstructive Lung Diseases in 2022: Time to “Unplug” from Our Daily Routine!

“…Mucus harbors unique biophysical properties, including viscoelasticity, an adjustable rheology, and a self-repairing capacity. Mucus is, therefore, an ideal medium for trapping and immobilizing external pathogens and toxins [ 1 ]. This important role explains the evolutionary conservation of mucus across various species from corals to humans [ 2 ].…”

“…Several mechanisms have been proposed to underlie these observations, including: (1) an obvious effect of past or current cigarette smoke exposure on airway remodeling (goblet cell hyperplasia and metaplasia) [ 21 , 24 ], on mucus production/secretion (particularly via the epidermal growth factor receptor (EGFR) [ 9 , 25 , 26 ]), and on mucus hydration [ 27 , 28 , 29 ]. (2) A qualitative alteration of the mucin network, enhanced in the contexts of chronic infection and/or acute exacerbations [ 1 , 30 , 31 , 32 ]. (3) An impairment in mucociliary clearance that could deteriorate in cases with ciliary motility dysfunction [ 33 ].…”