Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis.
chondroitin sulfate
eNOS
intestinal dysbiosis
necrotizing enterocolitis
Journal
Physiological reports
ISSN: 2051-817X
Titre abrégé: Physiol Rep
Pays: United States
ID NLM: 101607800
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
14
08
2023
received:
14
07
2023
accepted:
16
08
2023
medline:
13
9
2023
pubmed:
12
9
2023
entrez:
11
9
2023
Statut:
ppublish
Résumé
Necrotizing enterocolitis (NEC) continues to be a devastating disease in preterm neonates and has a paucity of medical management options. Chondroitin sulfate (CS) is a naturally occurring glycosaminoglycan (GAG) in human breast milk (HM) and has been shown to reduce inflammation. We hypothesized that supplementation with CS in an experimental NEC model would alter microbial diversity, favorably alter the cytokine profile, and (like other sulfur compounds) improve outcomes in experimental NEC via the eNOS pathway. NEC was induced in 5-day-old pups. Six groups were studied (n = 9-15/group): (1) WT breastfed and (2) Formula fed controls, (3) WT NEC, (4) WT NEC + CS, (5) eNOS KO (knockout) NEC, and (6) eNOS KO NEC + CS. Pups were monitored for clinical sickness score and weights. On postnatal day 9, the pups were killed. Stool was collected from rectum and microbiome analysis was done with 16 s rRNA sequencing. Intestinal segments were examined histologically using a well-established injury scoring system and segments were homogenized and analyzed for cytokine profile. Data were analyzed using GraphPad Prism with p < 0.05 considered significant. CS supplementation in formula improved experimental NEC outcomes when compared to NEC alone. CS supplementation resulted in similar improvement in NEC in both the WT and eNOS KO mice. CS supplementation did not result in microbial changes when compared to NEC alone. Our data suggest that although CS supplementation improved outcomes in NEC, this protection is not conferred via the eNOS pathway or alteration of microbial diversity. CS therapy in NEC does improve the intestinal cytokine profile and further experiments will explore the mechanistic role of CS in altering immune pathways in this disease.
Identifiants
pubmed: 37697223
doi: 10.14814/phy2.15819
pmc: PMC10495347
doi:
Substances chimiques
Chondroitin Sulfates
9007-28-7
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15819Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK133418
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD105301
Pays : United States
Informations de copyright
© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
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