title: Dietary GD3 ganglioside reduces the incidence and severity of necrotizing enterocolitis by sustaining regulatory immune responses.
abstract: OBJECTIVE
  Gangliosides are glycosphingolipids, rich in colostrum and in membrane microdomains, which promote enterocyte growth and differentiation, and modulate TH1/TH2 responses. In an in vitro intestinal explant model of necrotizing enterocolitis (NEC), gangliosides have been shown to ameliorate intestinal injury; however, possible immunomodulatory mechanisms associated with this observation, as well as potential in vivo protective effects of gangliosides, remain unknown. The present study evaluates the effects of dietary GD3, the predominant ganglioside in neonatal rat intestine, both on the clinicopathologic expression of disease and on ileal Foxp3+ T regulatory cell immune responses in an experimental NEC model.
  
  
  METHODS
  Newborn rat pups were fed gavage formula (NEC) or formula supplemented with 15 μg/mL GD3 (GD3-NEC). Dam-fed (DF) littermates served as controls. NEC was induced by asphyxia and cold stress. At 96 hours, ileal gross and histologic changes were evaluated, and ileal cytokine profiles, Foxp3 expression, and Foxp3+ cell numbers were determined.
  
  
  RESULTS
  GD3 decreased the incidence and gross and histopathologic severity of NEC. Ileal Foxp3 expression and Foxp3+ cell numbers were significantly decreased in the NEC group compared with DF. GD3 increased ileal Foxp3 expression and Foxp3+ cell numbers, in association with upregulation of anti-inflammatory cytokine interleukin (IL)-10 and chemokines, tissue inhibitor of metalloproteinases 1, IL-1 receptor antagonist (IL-1ra), and suppressed proinflammatory mediators.
  
  
  CONCLUSIONS
  These data suggest that dietary GD3 protects newborn rats from NEC, in part, by augmenting mucosal Foxp3+ T regulatory immune responses.
authors.affiliation: *Departments of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition †Department of Pathology, SUNY-Downstate Medical Center, Brooklyn, NY.
authors.forename: Jiliu
authors.initials: J
authors.lastname: Xu
authors.forename: Virginia
authors.initials: V
authors.lastname: Anderson
authors.forename: Steven M
authors.initials: SM
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D003126:Colostrum / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D018450:Disease Progression; D020345:Enterocolitis, Necrotizing / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005732:Gangliosides / Q000627:therapeutic use*; D007082:Ileum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007155:Immunologic Factors / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D005732:Gangliosides; D007155:Immunologic Factors; C026226:ganglioside, GD3