Role of postnatal acquisition of the intestinal microbiome in the early development of immune function.

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-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: Reed A Dimmitt, Elizabeth M Staley, Gin Chuang, Scott M Tanner, Thomas D Soltau, Robin G Lorenz
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 51 Issue 3 Pg. 262-73 (Sep 2010) ISSN: 1536-4801 [Electronic] United States
• PMID: 20639773 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cytokines
• Interleukin-17
• Toll-Like Receptors
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Animals, Newborn
• Anti-Bacterial Agents (pharmacology)
• Bacterial Translocation
• CD4-Positive T-Lymphocytes (metabolism)
• Cytokines (metabolism)
• Gastrointestinal Tract (drug effects, immunology, microbiology)
• Immune System (cytology, physiology)
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Interleukin-4 (metabolism)
• Intestinal Mucosa (drug effects, immunology)
• Lymph Nodes (immunology)
• Mice
• Mice, Inbred C57BL
• Reverse Transcriptase Polymerase Chain Reaction
• Spleen (immunology)
• T-Lymphocytes (metabolism)
• Toll-Like Receptors (metabolism)