ovalbumin and Infant--Newborn--Diseases

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)-α, 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-α 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.

Topics: Administration, Oral; Animals; Animals, Newborn; Bifidobacterium bifidum; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Microbiome; Humans; Hypersensitivity; Immunoglobulin E; Infant, Newborn; Infant, Newborn, Diseases; Interleukin-10; Interleukin-6; Intestines; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Probiotics; Tumor Necrosis Factor-alpha

Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period.. Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specific IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers.. Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

Topics: Allergens; Animals; Animals, Newborn; B-Lymphocytes; CD40 Antigens; Cytokines; Female; Fetal Development; Humans; Hypersensitivity; Immunity, Maternally-Acquired; Immunization; Immunoglobulin E; Infant, Newborn; Infant, Newborn, Diseases; Lymphocyte Activation; Maternal Exposure; Mice; Mice, Inbred BALB C; Ovalbumin; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, IgE; Receptors, IgG; T-Lymphocytes; Up-Regulation