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Continuous Liquid-Liquid Extraction of Medium-Chain Fatty Acids from Fermentation Broth Using Hollow-Fiber Membranes
Published on: August 9, 2024
Medium-chain fatty acid and its derivative impact mucus properties and vary with age and gestational maturity
J S Mortensen1, L S Krog1, S S-R Bohr2
1Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Abstract:
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.
Insights
Medium-chain fatty acids (MCFAs) enhance the intestinal mucus barrier function, particularly in younger and older pigs. This lipid-based approach offers a promising strategy for improving gut health across different life stages.
Area of Science:
- Gastroenterology
- Mucosal Immunology
- Nutritional Science
Background:
- The intestinal mucus layer is a crucial defense against pathogens.
- Mucus barrier integrity is compromised in early and late life stages.
- Medium-chain fatty acids (MCFAs) can potentially strengthen the mucus barrier.
Purpose of the Study:
- To investigate the effect of MCFAs on intestinal mucus barrier properties in pigs of varying ages.
- To determine how gestational maturity influences mucus barrier function and response to MCFAs.
- To elucidate the role of sialic acid in the interaction between MCFAs and mucus.
Main Methods:
- Ex vivo analysis of porcine intestinal mucus from pigs aged 5 days to 4 months.
- Measurement of pathogen marker diffusion and mucus viscosity.
- Assessment of mucus physicochemical properties (osmolality, protein, sialic acid content).
- Evaluation of the impact of sodium decanoate (C10) and salcaprozate sodium (SNAC) on mucus properties.
- Analysis of mucus viscosity changes after sialic acid cleavage.
Main Results:
- Pathogen marker diffusion decreased with increasing pig age and gestational immaturity.
- MCFAs (C10) and SNAC significantly increased mucus viscosity and reduced pathogen diffusion.
- These effects were more pronounced in mucus from older and gestationally immature pigs.
- Mucus properties varied with donor pig age and gestational maturity.
- Cleavage of mucin-bound sialic acids reduced the viscosity-enhancing effect of C10 and SNAC.
Conclusions:
- Intestinal mucus barrier properties and the efficacy of MCFAs are significantly influenced by age and gestational maturity.
- Sialic acid plays a key role in the interaction between MCFAs and the mucus barrier.
- Tailored nutritional and therapeutic strategies targeting specific age periods are needed for optimal gut health.
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