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Background: An altered compositional signature and reduced diversity of early gut microbiota are linked to development of allergic disease. We investigated the relationship between dominant Bifidobacterium species during the early post-natal period and subsequent development of allergic disease in the first year of life., Methods: Faecal samples were collected at age 1 week, 1 month and 3 months from 117 infants at high risk of allergic disease. Bifidobacterium species were analysed by quantitative PCR and terminal restriction fragment length polymorphism. Infants were examined at 3, 6 and 12 months, and skin prick test was performed at 12 months. Eczema was diagnosed according to the UK Working Party criteria., Results: The presence of B. catenulatum at 3 months was associated with a higher risk of developing eczema (OR adj = 4.5; 95% CI: 1.56-13.05, p adj = 0.005). Infants colonized with B. breve at 1 week (OR adj = 0.29; 95% CI: 0.09-0.95, p adj = 0.04) and 3 months (OR adj = 0.15; 95% CI: 0.05-0.44, p adj = 0.00001) had a reduced risk of developing eczema. Furthermore, the presence of B. breve at 3 months was associated with a lower risk of atopic sensitization at 12 months (OR adj = 0.38; 95% CI: 0.15-0.98, p adj = 0.05). B. breve colonization patterns were influenced by maternal allergic status, household pets and number of siblings., Conclusions: Temporal variations in Bifidobacterium colonization patterns early in life are associated with later development of eczema and/or atopic sensitization in infants at high risk of allergic disease. Modulation of the early microbiota may provide a means to prevent eczema in high-risk infants., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro-allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non-microbial stimuli in infants at high risk of allergic disease and their associations with development of allergic disease in the first year., Methods: Cord blood mononuclear cells from 72 neonates were cultured with toll-like receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat-killed Lactobacillus rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti-CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation to allergic disease outcomes during the first year of life (eczema and atopic sensitization)., Results: Infants with eczema (n = 24) had reduced percentages of FoxP3(hi)CD25(hi) Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p = 0.02) stimulated cultures as well as reduced IL-10 (p = 0.01) production following HKL stimulation compared to those without eczema (n = 48). No differences in Treg or cytokine responses to LPS, OVA or anti-CD3 were seen. Infants who developed sensitization had lower percentages of Treg following TLR2 stimulation (but not other stimuli) compared to non-sensitized infants., Conclusions: High-risk children who develop allergic disease in the first year of life have deficient Treg responses to microbial stimuli but not allergen from the time of birth, which may contribute to failure of immune tolerance development in infancy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The overall beneficial effects of breastfeeding for infants have been well documented, but its role in allergy prevention is controversial., Objective: We investigated the relationship between breast milk immunomodulatory factors and subsequent development of eczema and atopic sensitization in the first year of life., Methods: Day 7 and 28 breast milk samples were collected from mothers carrying infants at high risk of allergic disease. Aqueous-phase breast milk samples were assayed for TGF-β1, sCD14 and total IgA. Infants were assessed for the presence of eczema and atopic sensitization at 12 months of age. The levels of breast milk TGF-β1, sCD14 and total IgA were compared in infants who subsequently developed eczema and sensitization in the first year and those who did not., Results: The levels of breast milk sCD14, total IgA, and TGF-β1 at either day 7 or 28 were not associated with subsequent development of eczema or atopic sensitization during the first year of life., Conclusion: Levels of breast milk immune parameters were not associated with eczema outcomes or sensitization in infants at 12 months. This suggests that apparent immunological effects on breast milk immunomodulatory factors may not necessarily lead to clinical benefits, and these immune markers may not be critical determinants of allergic disease in infancy., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: Alterations in intestinal microflora have been linked to the development of allergic disease. Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains., Objectives: We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life., Methods: Fecal samples were collected 1 wk after birth from 98 infants at high risk of allergic disease, who were followed prospectively to age 12 months. Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism (T-RFLP) using restriction enzymes Sau96I and AluI, with a greater number of peaks representing greater diversity of bacterial communities., Results: Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema (AluI mean number of peaks 13.1 vs. 15.5, p = 0.003, 95% CI for difference in means -3.9, -0.8; Sau96I 14.7 vs. 17.2, p = 0.03, 95% CI -4.9, -0.3). No differences were observed for atopic compared to non-atopic infants, or infants with two allergic parents compared to those with one or no allergic parent., Conclusions: A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease. Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

We have recently shown that maternal administration of Lactobacillus rhamnosus GG (LGG) during late pregnancy can have beneficial effects on the early development of infant gut microbiota, promoting a bifidobacteria profile similar to that of a healthy breastfed infant. It is uncertain, however, whether such probiotic supplementation could influence the diversity of infant gut microbiota. We investigated the effect of pre-natal LGG on gut microbial diversity in the early post-natal period. Day-7 faecal samples were collected from 98 infants at high risk of allergic disease, whose mothers participated in a pre-natal probiotic eczema prevention study. Faecal microbial diversity was assessed by terminal restriction fragment length polymorphism using restriction enzymes Sau96I and AluI. A greater number of peaks represent greater diversity of bacterial communities. Administration of LGG to mothers during late pregnancy had no effects on the mean number of peaks in faecal samples from 1-wk-old infants as compared to placebo (AluI 14.4 vs. 15.5, p = 0.17, 95% CI -0.4, 2.5; Sau96I 17.3 vs. 15.8, p = 0.15, 95% CI -3.5, 0.5). Prenatal LGG failed to modulate diversity of early infant gut microbiota despite promoting a beneficial bifidobacteria profile., (© 2011 John Wiley & Sons A/S.)