Medium-chain fatty acid and its derivative impact mucus properties and vary with age and gestational maturity.

The intestinal mucus is a critical component of human health, acting as the first line of defense against pathogens. Yet, mucus has been reported to be more permeable and thus less of a barrier to pathogens both earlier and later in life. Lipids and their digestion products, such as medium-chain fatty acids (MCFAs), can strengthen the mucus barrier thereby reducing pathogen diffusion. Herein, the diffusion of a pathogen marker in ex vivo porcine intestinal mucus decreased with increasing pig age (5-day to 4-month) and gestational immaturity (term vs preterm). Upon the addition of the MCFA sodium decanoate (C10) as well as salcaprozate sodium (SNAC), an MCFA derivative, mucus' viscosity increased ≥7-fold and, importantly, the pathogen marker diffusion in the mucus decreased significantly. Interestingly, this effect was substantially more pronounced in mucus from older and from gestationally immature pigs. Relevant physicochemical properties of mucus (osmolality, protein and sialic acid contents) changed depending on the age and gestational maturity of the donor pigs. Notably, we found that cleavage of mucin-bound sialic acids resulted in a 3-4-fold lower effect of C10 and SNAC on mucus viscosity, establishing a direct link between the mucin-bound sialic acid and mucus' interaction with the MCFA and derivative. Overall, these findings demonstrate that the properties of the mucus barrier and the protective effects lipids like MCFAs are highly influenced by age and gestational maturity. Therefore, our results highlight the need for nutrition and therapeutic strategies tailored to specific age periods to ensure optimal gut health.