Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: sub-sample analysis from a RCT.

Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.

Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization?

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clear; efficacy may depend on the timing, dose, duration, and specific probiotic used. Using a double-blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high-risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema at 2 and 4 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no significant effect. OBJECTIVE: To determine whether differences in effects of HN001 and HN019 on eczema persist to age 6 years, and to investigate effects on sensitization. METHODS: Standard procedures were used to assess eczema (The UK Working Party's Criteria), eczema severity (SCORAD), atopic sensitization [skin prick tests (SPT), total and specific IgE] and standard questions used for asthma, wheeze, and rhinoconjunctivitis. RESULTS: HN001 was associated with significantly lower cumulative prevalence of eczema (HR = 0.56, 95% CI 0.39-0.80), SCORAD ≥ 10 (HR = 0.69, 0.49-0.98) and SPT sensitization (HR = 0.69, 95% CI 0.48-0.99). The point prevalence of eczema (RR = 0.66, 95% CI 0.44-1.00), SCORAD ≥ 10 (RR = 0.62, 95% CI 0.38-1.01) and SPT sensitization (RR = 0.72, 95% CI 0.53-1.00) were also reduced among children taking HN001. HN019 had no significant effect on any outcome. CONCLUSION AND CLINICAL RELEVANCE: This study provides evidence for the efficacy of the probiotic L. rhamnosus HN001 in preventing the development of eczema and possibly also atopic sensitization in high risk infants to age 6 years. The absence of a similar effect for HN019 indicates that benefits may be species specific.

A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years.

BACKGROUND: Using a double blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema by age 2 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no effect. OBJECTIVE: The aim of this study was to investigate the associations of HN001 and HN019 with allergic disease and atopic sensitization among these children at age 4 years, 2 years after stopping probiotic supplementation. METHODS: The presence (UK Working Party's Diagnostic Criteria) and severity SCORing Atopic Dermatitis (SCORAD) of eczema and atopy (skin prick tests) and parent-reported symptoms of asthma and rhinoconjunctivitis were assessed using standard protocols and questions. RESULTS: Four-hundred and seventy-four infants were eligible at birth of whom 425 (90%) participated in this follow-up. The cumulative prevalence of eczema by 4 years (Hazard ratio (HR) 0.57 (95% CI 0.39-0.83)) and prevalence of rhinoconjunctivitis at 4 years (Relative risk 0.38 (95% CI 0.18-0.83)) were significantly reduced in the children taking HN001; there were also nonsignificant reductions in the cumulative prevalence of SCORAD ≥ 10 (HR 0.74 (95% CI 0.52-1.05), wheeze (HR 0.79 (95% CI 0.59-1.07)) and atopic sensitization (HR = 0.72 (95% CI 0.48-1.06)). HN019 did not affect the prevalence of any outcome. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that the protective effect of HN001 against eczema, when given for the first 2 years of life only, extended to at least 4 years of age. This, together with our findings for a protective effect against rhinoconjunctivitis, suggests that this probiotic might be an appropriate preventative intervention for high risk infants.

Selenium status and allergic disease in a cohort of New Zealand children.

BACKGROUND: New Zealand has one of the highest rates of asthma and atopy. Selenium has been implicated in the aetiology of asthma, and associations between low selenium status and asthma in New Zealand children have been reported. OBJECTIVE: The aim was to investigate the association between selenium status and allergic disease in a birth cohort of New Zealand children. METHODS: The New Zealand Asthma and Allergy Cohort Study is a prospective birth cohort in Wellington and Christchurch, involving 1105 infants born 1997-2001. During the 6-year assessment (n = 635), associations were investigated between plasma selenium (PlSe) and whole blood glutathione peroxidase activity (WBGPx) and allergy-related health outcomes including asthma, wheeze, hayfever, rhinitis, eczema and rash. RESULTS: Wellington children had greater PlSe and WBGPx than Christchurch children (P < 0.001 for both). PlSe (P = 0.004) and WBGPx (P = 0.03) were lower in children exposed to environmental smoke, but differences were no longer significant after adjustment for study location, current household smoking (5-6 years), maternal smoking during pregnancy, family history (either parent with asthma, eczema or hayfever), prioritized ethnicity (Maori, Pacific peoples, Other, European), gender, season born, number of siblings, New Zealand Deprivation Index and body mass index at 6 years. Analysis of PlSe or WBGPx as continuous variables or of quartiles of PlSe with health outcomes showed no significant associations after adjustment. Univariate analysis of quartiles of PlSe and WBGPx with persistent wheeze showed significant inverse trends (P = 0.005 for both), but these reduced after adjustment. CONCLUSIONS AND CLINICAL RELEVANCE: Our results do not support a strong association between selenium status and the high incidence of asthma in New Zealand. However, there was a modest association between lower PlSe and WBGPx activity and higher incidence of persistent wheeze.

Antibiotic use in early childhood and the development of asthma.

BACKGROUND AND OBJECTIVE: Recent investigations have focused on the role of infections in infancy in promoting or protecting against the subsequent development of asthma. A related hypothesis concerns the possible role of medical responses to infections, including the widespread use of antibiotics. We chose children at Rudolf Steiner schools to test this latter hypothesis because a significant proportion of parents rejects the use of conventional treatments, including antibiotics. METHODS: Seventy-five per cent (n = 456) of parents of children aged 5-10 years attending Rudolf Steiner schools throughout New Zealand completed questionnaires which included questions on the use of antibiotics and a history of asthma and wheeze in their children. RESULTS: After controlling for potential confounders, antibiotic use was significantly associated with having a history of asthma (OR = 2.74, 95% CI: 1.10-6.85) or wheeze (OR = 1. 86, 95% CI: 1.06-3.26) but not with current wheeze (OR = 1.08, 95% CI: 0.54-2-16). The adjusted odds ratio for asthma was 4.05 (95% CI: 1.55-10.59) if antibiotics were used in the first year of life and 1. 64 (95% CI: 0.60-4.46) if antibiotics had been used only after the first year of life when compared with children who had never used antibiotics. The number of courses of antibiotics during the first year of life was also associated with increased odds ratios for asthma: 2.27 (95% CI: 1.14-4.51) for one to two courses and 4.02 (95% CI: 1.57-10.31) for three or more courses when compared with no antibiotic use in the first year of life. Although not significant, the association of antibiotics and hay fever (OR = 1.99 [95% CI: 0. 93-4.26]) was of a similar strength to the association of antibiotics with a history of wheeze. Antibiotics were not significantly associated with eczema (OR = 1.23 [95% CI: 0.71-2.13]). CONCLUSION: Antibiotic use in infancy may be associated with an increased risk of developing asthma. Further study is required to determine the reasons for this association.