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Published on: January 9, 2026
Role of postnatal acquisition of the intestinal microbiome in the early development of immune function
Reed A Dimmitt1, Elizabeth M Staley, Gin Chuang
1Department of Microbiology, University of Alabama, Birmingham, AL, USA.
Insights
Early life exposure to antibiotics reduces gut bacteria, impairing immune system development in mice. This microbial reduction impacts T-cell function and increases bacterial translocation, highlighting the importance of the gut microbiome for infant immunity.
Area of Science:
- Immunology
- Microbiology
- Neonatal Medicine
Background:
- Broad-spectrum antibiotics in premature infants disrupt gut microbiota, potentially contributing to necrotizing enterocolitis.
- Probiotic use in premature infants is associated with reduced necrotizing enterocolitis incidence.
- The gut microbiome's role in postnatal immune system development is hypothesized to be a key mechanism.
Purpose of the Study:
- To investigate the influence of commensal gut microbiota on the postnatal development of the mucosal immune system.
- To compare immune responses in specific pathogen-free versus microbial-reduced (antibiotic-treated) mice.
Main Methods:
- Real-time PCR to assess immune molecule and microbial sensor expression in the mouse gastrointestinal tract.
- Comparison of specific pathogen-free and microbial-reduced mice regarding immune markers, T-cell populations, intestinal barrier function, and T-cell phenotype.
- Analysis included Toll-like receptor expression, bacterial translocation, lymphocyte counts, and cytokine production.
Main Results:
- Microbial-reduced mice showed decreased expression of Toll-like receptors 2, 4, and 5.
- Increased bacterial translocation across the intestinal barrier was observed in microbial-reduced mice, despite normal tight-junctional function.
- Microbial-reduced mice exhibited fewer splenic B cells and mesenteric lymph node CD4+ T cells, with systemic T cells showing a T-helper type 2 phenotype (increased IL-4, decreased IFN-gamma and IL-17).
Conclusions:
- Intestinal commensal microbiota significantly influence early postnatal immune development.
- Identifying specific bacteria or ligands involved could elucidate how antibiotic and probiotic therapies affect mucosal immunity and related diseases.
- This research provides insight into the critical role of the gut microbiome in shaping the developing immune system in early life.
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.
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