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• CFTR-deficient pigs present increased lung mucin sialylation at birth in the absence of inflammation. • Increased mucin sialylation is linked to increased pseudomonas aeruginosa adhesion to mucins. • CF pigs also present a mucociliary clearance defect, in the absence of inflammation, which may contribute bacterial colonization and development of early lung disease. These defects seems to be linked to the absence of CFTR functionality since they are independent of an inflammatory environment in the lungs. Bacterial colonization in cystic fibrosis (CF) lungs has been directly associated to the loss of CFTR function, and/or secondarily linked to repetitive cycles of chronic inflammation/infection. We hypothesized that altered molecular properties of mucins could contribute to this process. Newborn CFTR+/+ and CFTR−/− were sacrificed before and 6 h after inoculation with luminescent Pseudomonas aeruginosa into the tracheal carina. Tracheal mucosa and the bronchoalveolar lavage (BAL) fluid were collected to determine the level of mucin O-glycosylation, bacteria binding to mucins and the airways transcriptome. Disturbances in mucociliary transport were determined by ex-vivo imaging of luminescent Pseudomonas aeruginosa. We provide evidence of an increased sialylation of CF airway mucins and impaired mucociliary transport that occur before the onset of inflammation. Hypersialylation of mucins was reproduced on tracheal explants from non CF animals treated with GlyH101, an inhibitor of CFTR channel activity, indicating a causal relationship between the absence of CFTR expression and the sialylation of mucins. This increased sialylation was correlated to an increased adherence of P. aeruginosa to mucins. In vivo infection of newborn CF piglets by live luminescent P. aeruginosa demonstrated an impairment of mucociliary transport of this bacterium, with no evidence of pre-existing inflammation. Our results document for the first time in a well-defined CF animal model modifications that affect the O-glycan chains of mucins. These alterations precede infection and inflammation of airway tissues, and provide a favorable context for microbial development in CF lung that hallmarks this disease. [ABSTRACT FROM AUTHOR]

• The effects of host immune factors on mucin glycosylation are summarized. • Key gut microbes associated with mucin glycosylation are discussed. • The regulative mechanisms of dietary components on mucin glycosylation are proposed. • Personalized anti-disease strategies targeting mucin glycosylation are brought forward. Intestinal mucins glycosylation is regulated by host cues and environmental signals from the microbiome and diets. However, the mechanisms responsible for the dialogue between these three factors and mucin glycosylation in the digestive environment of the host are not well understood. In this review, the dynamic alterations of mucin glycosylation induced by immune responses to gut diseases are summarized. The various types of interactions between mucin glycans and gut microbes, including adhesins, glycosidases, metabolic products and surface components, are discussed. The mechanisms that determine how dietary components (fat, fiber, prebiotics, protein, and food additives) affect intestinal mucin glycosylation and maintain mucosal homeostasis are identified. A potential framework for individualized dietary recommendations is proposed for the prevention of abnormal mucin glycosylation driven by immune dysregulation, gut microbiome alterations and other factors. This review may provide a basis for future research on glycosylation-inspired therapies for gut diseases. [ABSTRACT FROM AUTHOR]