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-gamma 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.
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-gamma 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.
Authors: Andrew R Barclay; Ben Stenson; Judith H Simpson; Lawrence T Weaver; David C Wilson Journal: J Pediatr Gastroenterol Nutr Date: 2007-11 Impact factor: 2.839
Authors: Francois-Pierre J Martin; Yulan Wang; Norbert Sprenger; Ivan K S Yap; Torbjörn Lundstedt; Per Lek; Serge Rezzi; Ziad Ramadan; Peter van Bladeren; Laurent B Fay; Sunil Kochhar; John C Lindon; Elaine Holmes; Jeremy K Nicholson Journal: Mol Syst Biol Date: 2008-01-15 Impact factor: 11.429
Authors: Scott M Tanner; Taylor F Berryhill; James L Ellenburg; Tamas Jilling; Dava S Cleveland; Robin G Lorenz; Colin A Martin Journal: Am J Pathol Date: 2014-11-04 Impact factor: 4.307
Authors: Aaron A Reeves; Marney C Johnson; Margarita M Vasquez; Akhil Maheshwari; Cynthia L Blanco Journal: Breastfeed Med Date: 2013-07-19 Impact factor: 1.817
Authors: Brandie D Wagner; Marci K Sontag; J Kirk Harris; Joshua I Miller; Lindsey Morrow; Charles E Robertson; Mark J Stephens; Brenda B Poindexter; Steven H Abman; Peter M Mourani Journal: J Matern Fetal Neonatal Med Date: 2017-11-28