Neonatal formula feeding leads to immunological alterations in an animal model of type 1 diabetes

Pediatr Res. 2008 Mar;63(3):303-7. doi: 10.1203/PDR.0b013e31815ed662.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aging / immunology
  • Animal Nutritional Physiological Phenomena*
  • Animals
  • Animals, Newborn
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Food, Formulated*
  • Forkhead Transcription Factors / metabolism
  • Immunity, Mucosal
  • Inflammation Mediators / metabolism
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Intestines / immunology
  • Lactation*
  • Liver / immunology
  • Male
  • Rats
  • Rats, Inbred BB
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Thymus Gland / immunology


  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, rat
  • Inflammation Mediators
  • Interleukin-2 Receptor alpha Subunit