Age-related remodeling of the intestinal mucus barrier in pigs: implications for post-weaning diarrhea

The intestinal mucus barrier plays a central role in maintaining intestinal integrity, yet its development during early life and weaning in pigs remain incompletely understood. This study characterized age-related changes in goblet cell populations and mucus properties and investigated their association with diarrhea. Thirty Danish crossbred piglets from a longitudinal cohort were stratified by age (4, 14, 25, 49, and 67 days) and diarrhea status (cases vs. controls). Jejunal and colonic tissues were evaluated by histology and immunohistochemistry for MUC2 and MUC5AC, while mucus glycosylation was assessed using the bacteria-derived mucin-binding probe X409. Digital image analysis was performed at crypt level. Marked age-dependent remodeling occurred in both intestinal segments. Crypt-villus unit depth and goblet cell abundance generally increased with age, accompanied by age-related changes in MUC2 and X409-labeling. X409 staining intensity varied with age and position along the crypt-villus axis, indicating age-dependent changes in the spatial distribution of mucus-associated O-glycosylation. Disease-associated differences were limited. In jejunum at 67 days of age, cases had fewer luminal goblet cells and reduced X409 labeling than controls, while colonic crypt depth differed between cases and controls at selected ages. No MUC5AC expression was observed. These findings demonstrate substantial age-dependent quantitative and qualitative remodeling of the intestinal mucus barrier during postnatal development. Limited disease-associated differences suggest that diarrhea was not characterized by widespread alterations in mucus properties, although localized differences, particularly in older piglets, may be associated with intestinal vulnerability. These results highlight the importance of mucus barrier maturation during the developmental period arround weaning.