Oral administration of Bifidobacterium bifidum TMC3115 to neonatal mice may alleviate IgE-mediated allergic risk in adulthood

摘要

This study aimed to demonstrate whether exposure to bifidobacteria during early life influences immunity and alleviates the risk of immunoglobulin E (IgE)-mediated allergies in adulthood. BALB/c neonatal mice (n=54) were administered with a lyophilised cell preparation of Bifidobacterium bifidum TMC3115 (TMC3115) for 3 weeks. Following the intervention, the mice were immunised with intraperitoneal ovalbumin (OVA). The morphology and function of the intestinal epithelium were determined using histopathological examinations. Intestinal microbiota was detected using quantitative PCR and characterised using next-generation sequencing of 16S rRNA genes from faecal DNA. Caecal short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry. Serum levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and immunoglobulin E (IgE) and the percentage of splenic CD4+ T cells were examined using enzyme-linked immunosorbent assay and flow cytometry, respectively. TMC3115 did not significantly affect body weight, and cause any severe systemic inflammation or other clinical symptoms among the neonatal or adult mice, although the crypt depths and Muc2-positive cells in some intestinal segments of neonatal mice were significantly lower than control. Oral TMC3115 administration significantly increased faecal microbial diversity, relative abundance of Bacteroidetes and caecal SCFAs production in neonatal mice. Following the intervention, neonatal mice treated with TMC3115 exhibited less increase in serum IgE levels induced by OVA in adults and significantly higher TNF-alpha and IL-10 levels than in control. Our findings indicate that the oral administration of bifidobacteria, particularly certain strains, such as TMC3115, during early life could alleviate the risk of IgE-mediated allergies in adult host animals. Modifications of intestinal microbiota, SCFAs metabolism and anti-inflammatory cytokine IL-10 production by bifidobacteria may at least in part be a key mechanism underlying the effect of bifidobacteria on the IgE-mediated immune sensitivity of hosts to attacks by allergens at both neonatal and adult stages.