title: Neonatal formula feeding leads to immunological alterations in an animal model of type 1 diabetes.
abstract: Neonatal diet may influence the development of type 1 diabetes (T1D) in susceptible individuals through an intestinal mucosal inflammatory response, resulting in loss of self-tolerance. We tested the hypothesis that formula feeding during the neonatal period accelerates the development of T1D in diabetes-prone BioBreeding (BBDP) rats through regulation of CD4+CD25+ regulatory T lymphocytes (T(reg)) and anti-inflammatory cytokines. BBDP rat pups fed rat milk substitute (RMS) via a "pup-in-the cup" system were compared with mother-fed (MF) rats. The spleen and thymus were analyzed for Foxp3-expressing CD4+/CD25+ T cells. Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and IL-18. Diabetes-free survival, time of disease onset, and T(reg)/total T lymphocyte ratios were not different. MF pups had higher ileal CINC (p < 0.001) and IL-18 (p = 0.002), but no differences in the liver. There were no differences in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had greater liver TNF-alpha (p < 0.001), IFN-gamma, and IL-4 (p < 0.01) and lower IL-10 (p = 0.002) compared with MF animals. Formula versus maternal milk altered the hepatic cytokine profile at 75 d toward an inflammatory pattern but did not result in altered T(reg) cell frequencies or the development of T1D.
authors: Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
authors: Ricardo A
authors: RA
authors: Caicedo
authors: Nan
authors: N
authors: Li
authors: Clotilde
authors: C
authors: Des Robert
authors: Philip O
authors: PO
authors: Scumpia
authors: Chad P
authors: CP
authors: Hubsher
authors: Clive H
authors: CH
authors: Wasserfall
authors: Desmond A
authors: DA
authors: Schatz
authors: Mark A
authors: MA
authors: Atkinson
authors: Josef
authors: J
authors: Neu
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005526:Food, Formulated; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018928:Immunity, Mucosal; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007422:Intestines / Q000276:immunology; D007774:Lactation; D008099:Liver / Q000276:immunology; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit