Early gut colonization by Bifidobacterium breve and B. catenulatum differentially modulates eczema risk in children at high risk of developing allergic disease.

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 (ORadj = 4.5; 95% CI: 1.56-13.05, padj = 0.005). Infants colonized with B. breve at 1 week (ORadj = 0.29; 95% CI: 0.09-0.95, padj = 0.04) and 3 months (ORadj = 0.15; 95% CI: 0.05-0.44, padj = 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 (ORadj = 0.38; 95% CI: 0.15-0.98, padj = 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.

Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high-risk infants.

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.

Maternal Supplementation with LGG Reduces Vaccine-Specific Immune Responses in Infants at High-Risk of Developing Allergic Disease.

Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N = 31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.

Probiotic effects in allergic disease.

The increasing prevalence of allergic disease has been linked to reduced microbial exposure in early life. Probiotics have recently been advocated for the prevention and treatment of allergic disease. This article summarises recent publications on probiotics in allergic disease, focusing on clinical studies of prevention or treatment of allergic disease. Studies employing the combined administration of pre-natal and post-natal probiotics suggest a role for certain probiotics (alone or with prebiotics) in the prevention of eczema in early childhood, with the pre-natal component of treatment appearing to be important for beneficial effects. On the other hand, current data are insufficient to support the use of probiotics for the treatment of established allergic disease, although recent studies have highlighted new hope in this area. Probiotic bacteria continue to represent the most promising intervention for primary prevention of allergic disease, and well-designed definitive intervention studies should now be a research priority.

Relationship between breast milk sCD14, TGF-ß1 and total IgA in the first month and development of eczema during infancy.

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-ß1, 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-ß1, 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-ß1 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.

Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants.

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.

Oral immunotherapy for the treatment of food allergy.

Food allergies have increased significantly over recent decades and are the most common cause of admissions for anaphylaxis in childhood, particularly in children under 5 years of age. Current management of food allergy is limited to strict food allergen avoidance together with education on the recognition and emergency management of allergic reactions, and in some cases provision of self-injectable adrenaline. Although this supportive management approach is generally effective, it is burdensome for patients and families, and in turn leads to reduced quality of life. Patients with food allergy would benefit greatly from a definitive treatment that could achieve long-term tolerance. Recent studies demonstrate that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses. However, it remains uncertain whether long-term tolerance can be achieved with current OIT regimens. Increased allergen dose, duration of OIT and/or inclusion of an immune modifying adjuvant may enhance the tolerogenic potential of OLT. Allergic reactions during OIT are common, although severe reactions are infrequent. Oral immunotherapy holds promise as a novel approach to the definitive treatment of food allergy.

Prenatal administration of Lactobacillus rhamnosus has no effect on the diversity of the early infant gut microbiota.

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.

Infections in post-tsunami victims.

Two tsunami survivors from Banda Acheh, Sumatra, presented with pyrexia of unknown origin and a nonresolving left-sided empyema, respectively. Both children had mixed infections of tuberculosis and melioidosis; Salmonella typhi was also present in the second patient. Mixed infections are common late sequela complications in post-tsunami victims.