1138 Relationship Between Gut Microbiota in the First 3 Months of Life and Infant Immune Function at Age 12 Months

Wednesday, 14 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Intan Hakimah Ismail, MD, MMed , Department of Paediatrics, Universiti Putra Malaysia (UPM), Serdang, Malaysia

Paul Licciardi, PhD , Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, Australia

Frances Oppedisano, BAppSc , Infectious Diseases and Microbiology, Murdoch Childrens Research Institute, Melbourne, Australia

Robert Boyle, MB ChB, PhD , Department of Paediatrics, Imperial College London, London, United Kingdom

Roy Robins-Browne, MJB BCh, PhD , Infectious Diseases and Microbiology, Murdoch Childrens Research Institute, Melbourne, Australia

Mimi Tang, MBBS, PhD, FRACP, FRCPA , Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, Australia

Background: Distinctive pattern and diversity in early intestinal colonisation are shown to influence immune maturation and potentially development of allergic disease. We recently demonstrated that prenatal supplementation with Lactobacillus rhamnosus GG (LGG) during late pregnancy can influence infant gut colonisation by particular Bifidobacterium species directing towards healthy infant-type microbiota. We investigated whether this early-life gut colonisation with Bifidobacterium species is associates with systemic immune responses at 12 months of age.

Methods: Faecal samples were collected from infants during the first 3 months of life. Bacterial DNA was extracted from the faecal samples and Bifidobacterium longum, B. lactis, B. breve, B. angulatum, B adolescentis, and B. catenulatum were detected by real time PCR. Infants’ peripheral blood mononuclear cells at 12 months were stimulated with ovalbumin (OVA), heat-killed LGG (HKL) (the probiotic used in the original study), tetanus toxoid (TT), anti-CD3 or without stimulus. Cells were analysed by flow cytometry for markers of dendritic cells phenotype and regulatory T cell (Treg) numbers. Culture supernatants were analysed for IL-4, IL-6, IL-10, IL-13, IFN-γ and TNF-α by multiplex ELISA, while TGF-β1 and IL-12p40 were measured using ELISA.

Results: Colonisation with B. longum at day 7 of life was associated with significantly higher (p < 0.01) levels of Th1 cytokine (IFN-γ) and pro-inflammatory cytokines (IL-6 and TNF-α) and increased (p < 0.05) secretions of Th2 (IL-13) and regulatory cytokine (IL-10) in infants at 12 months. However, colonisation with B. adolescentis at day 3 was associated with higher secretion of IL-4 cytokine. A significantly increased numbers of Treg were observed in infants colonised with B. adolescentis at 7 days of age.

Conclusions: Colonisation with specific Bifidobacterium species in early life can influence cellular immune function, namely cytokine profiles and Treg later at 12 months. This suggests that probiotic treatment during pregnancy may modulate infant immune function as late as 12 months of age, feasibly mediated by modulation of infant microbiota. However, the immune mechanism that might protect against allergic disease is still unclear.