Abstract
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E. coli and E. cloacae) with developmental age and exposure to NEC stressors in Sprague Dawley rats. Early developmental age (5 day old) was characterized by a more permeable mucus layer relative to 21 day old pups, suggesting immaturity may contribute to exposure of the epithelium to microbes. Exposure to NEC stressors was associated with reduced mucus permeability, which may aid in survival. Feeding with breastmilk as opposed to formula reduces incidence of NEC. Thus, NEC-stressed (N-S) rat pups were orally dosed with breastmilk components lysozyme (N-S-LYS) or docosahexaenoic acid (N-S-DHA). N-S-LYS and N-S-DHA pups had a less permeable mucus barrier relative to N-S pups, which suggests the potential of these factors to strengthen the mucus barrier and thus protect against disease.
Highlights
IntroductionMucus is a dynamic barrier that is continuously secreted, degraded by the microbiome (e.g., mucin sugar cleavage)[17], and shed from the mucosal surface[18]
Mucus is a dynamic barrier that is continuously secreted, degraded by the microbiome[17], and shed from the mucosal surface[18]
The impact of developmental age (5do, 21do), exposure to Necrotizing enterocolitis (NEC) stressors (N-S), and prophylactic treatments (N-S-LYS, N-S-docosahexaenoic acid (DHA)) on intestinal mucus barrier properties was studied by analyzing the diffusion of particles and transport of bacteria (E. coli and E. cloacae) through an intact mucus layer on excised tissue
Summary
Mucus is a dynamic barrier that is continuously secreted, degraded by the microbiome (e.g., mucin sugar cleavage)[17], and shed from the mucosal surface[18]. We recently utilized MPT and time-lapse video microscopy of diffusing particles and swimming microbes to demonstrate that two breastmilk components, lysozyme (LYS) and docosahexaenoic acid (DHA), alter mucus barrier properties (i.e. decrease particle and microbe transport through healthy porcine intestinal mucus (data not published)). This finding motivates exploration of the impact of oral dosing of these agents on mucus barriers in rat pups exposed to NEC stressors. Orally dosed LYS and DHA inhibited Escherichia coli transport significantly in intestinal mucus of pups exposed to NEC stressors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
