Role of Postnatal Acquisition of the Intestinal Microbiome in the Early Development of Immune Function
- 1 September 2010
- journal article
- research article
- Published by Wiley in Journal of Pediatric Gastroenterology and Nutrition
- Vol. 51 (3), 262-273
- https://doi.org/10.1097/mpg.0b013e3181e1a114
Abstract
Objectives: Therapy with broad-spectrum antibiotics is a common practice for premature infants. This treatment can reduce the biodiversity of the fecal microbiota and may be a factor in the cause of necrotizing enterocolitis. In contrast, probiotic treatment of premature infants reduces the incidence of necrotizing enterocolitis. We hypothesized that 1 mechanism for these observations is the influence of bacteria on postnatal development of the mucosal immune system. Materials and Methods: Expression of immune molecules and microbial sensors was investigated in the postnatal mouse gastrointestinal tract by real-time polymerase chain reaction. Subsequently, 2-week-old specific pathogen-free and microbial-reduced (MR; antibiotic treated) mice were compared for immune molecule and microbial sensor expression, mesenteric lymph node T-cell numbers and activation, intestinal barrier function/permeability, systemic lymphocyte numbers, and T-cell phenotype commitment. Results: Toll-like receptor 2, 4, and 5 expression was highest in 2-week-old specific pathogen-free mice, and this expression was decreased in MR mice. There was no difference in intestinal tight-junctional function, as evaluated by fluorescein isothiocyanate-dextran uptake, but MR mice had increased bacterial translocation across the intestinal epithelial barrier. MR mice had significantly fewer splenic B cells and mesenteric lymph node CD4+ T cells, but there were normal numbers of splenic T cells. These systemic T cells from MR mice produced more interleukin-4 and less interferon-γ and IL-17, indicative of maintenance of the fetal, T-helper cell type 2 phenotype. Conclusions: The present study shows that intestinal commensal microbiota have an influence on early postnatal immune development. Determining specific bacteria and/or bacterial ligands critical for this development could provide insight into the mechanisms by which broad-spectrum antibiotics and/or probiotic therapy influence the development of the mucosal immune system and mucosal-related diseases.Funding Information
- National Institutes of Health (R01 DK059911, P01 DK071176, T32 AI07051, K08 HD46506, C06RR020136)
- American Asthma Foundation (06‐0167)
- Juvenile Diabetes Research Foundation United States of America (36‐2008‐930)
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