SummaryBackground Previous reports have suggested that certain probiotics given to mothers and children at risk of atopy halves the incidence of atopic dermatitis (AD) at 2 years of age. Objectives To examine if probiotics given to pregnant women in a nonselected population could prevent atopic sensitization or allergic diseases during the child's first 2 years. Methods In a randomized, double-blind trial of children from a nonselected maternal population (ClinicalTrials.gov identifier: NCT00159523), women received probiotic milk or placebo from 36 weeks of gestation to 3 months postnatally during breastfeeding. The probiotic milk contained Lactobacillus rhamnosus GG, L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12. Children with an itchy rash for more than 4 weeks were assessed for AD. At 2 years of age, all children were assessed for atopic sensitization, AD, asthma and allergic rhinoconjunctivitis. The intention-to-treat (ITT) analysis was enabled by multiple imputations. Results Four hundred and fifteen pregnant women were computer randomized. At 2 years, 138 and 140 children in the probiotic and the placebo groups, respectively, were assessed. In the ITT analysis, the odds ratio (OR) for the cumulative incidence of AD was 0AE51 in the probiotic group compared with the placebo [95% confidence interval (CI) 0AE30-0AE87; P = 0AE013]. There were no significant effects on asthma (OR 0AE68, 95% CI 0AE26-1AE80; P = 0AE437) or atopic sensitization (OR 1AE52, 95% CI 0AE74-3AE14; P = 0AE254). Conclusions Probiotics given to nonselected mothers reduced the cumulative incidence of AD, but had no effect on atopic sensitization.

Despite the importance, the diversity of the human infant gut microbiota still remains poorly characterized at the regional scale. Here, we investigated the faecal microbiota diversity in a large 16S rRNA gene data set from a healthy cohort of 86 mothers and their children from the Trondheim region in Norway. Samples were collected from mothers during early and late pregnancy, as well as from their children at 3 days, 10 days, 4 months, 1 year and 2 years of age. Using a combination of Sanger sequencing of amplicon mixtures (without cloning), real-time quantitative PCR and deep pyrosequencing, we observed a clear age-related colonization pattern in children that was surprisingly evident between 3- and 10-day samples. In contrast, we did not observe any shifts in microbial composition during pregnancy. We found that alpha-diversity was highest at 2 years and lowest at 4 months, whereas beta-diversity estimates indicated highest interindividual variation in newborns. Variation significantly decreased by the age of 10 days and was observed to be convergent over time; however, there were still major differences between 2 years and adults whom exhibited the lowest interindividual diversity. Taken together, the major age-affiliated population shift within gut microbiota suggests that there are important mechanisms for transmission and persistence of gut bacteria that remain unknown.

Fish consumption in infancy was more important than maternal fish intake during pregnancy in preventing eczema in childhood. The intake of fish per se, not specifically n-3 polyunsaturated fatty acids, was most important in preventing eczema.

BackgroundPerinatal probiotics supplementation has been shown to be effective in the primary prevention of atopic dermatitis (AD) in early childhood, although the long term effects of probiotics on AD and other allergic diseases is less certain. We have previously reported a significant reduction in the cumulative incidence of AD at 2 years after maternal probiotic supplementation. In this study we present the effects of perinatal probiotics given to women from a general population on allergy related diseases in their offspring at 6 years.MethodsFour hundred and fifteen pregnant women were randomised to receive probiotic or placebo milk in a double-blinded trial from 36 week gestation until 3 months postpartum. Probiotic milk contained Lactobacillus rhamnosos GG, L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12. At 6 years, children were re-assessed for AD, atopic sensitisation, asthma and allergic rhinoconjunctivitis (ARC).ResultsAt 6 years, 81 and 82 children were assessed for AD in the probiotic and placebo groups, respectively. In a multiple imputation analysis, there was as trend towards a lower cumulative incidence of AD in the probiotic group compared to the placebo group (OR 0.64, 95 % CI 0.39-1.07, p = 0.086; NNT = 10). This finding was statistically significantly in the complete case analysis (OR 0.48, 95 % CI 0.25-0.92, p = 0.027, NNT = 6). The prevalence of asthma and atopic sensitisation, and the cumulative incidence of ARC were not significantly affected by the probiotic regime at 6 years of age.ConclusionsMaternal probiotic ingestion alone may be sufficient for long term reduction in the cumulative incidence of AD, but not other allergy related diseases.Trial registrationClinicalTrials.gov identifier: NCT00159523Electronic supplementary materialThe online version of this article (doi:10.1186/s12895-015-0030-1) contains supplementary material, which is available to authorized users.

Transition from an infant to an adult associated gut microbiota with age through establishment of strict anaerobic bacteria remains one of the key unresolved questions in gut microbial ecology. Here a comprehensive comparative analysis of stool microbiota in a large cohort of mothers and their children sampled longitudinally up until 2 years of age using sequencing analysis tool was presented that allows realistic microbial diversity estimates. In this work, evidence for the switch from children to adult associated microbial profile between 1 and 2 years of age was provided, suggestively driven by Bifidobacterium breve. An Operational Taxonomic Unit (OTU) belonging to B. breve was highly prevalent in the population throughout the first year of life, and was negatively associated with detection of a range of adult-like OTUs. Although an adult profile was not fully established by 2 years of age, it was demonstrated that with regards to the most prevalent OTUs, their prevalence in the child population by then already resembled that of the adult population. Taken together, it was proposed that late-colonizing OTUs were recruited at a later stage and were not acquired at birth with the recruitment being controlled by gatekeeping OTUs until the age of 1 year.

Different probiotic bacteria seem to have different ability to transfer from the mother to the child. We found no evidence that the probiotics altered the microbial composition or α- and β-diversity of the children.

BackgroundPerinatal probiotic ingestion has been shown to prevent atopic dermatitis (AD) in infancy in a number of randomised trials. The Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT) trial involved a probiotic supplementation regime given solely to mothers in the perinatal period and demonstrated a ~40% relative risk reduction in the cumulative incidence of AD at 2 years of age. However, the mechanisms behind this effect are incompletely understood. Micro-RNAs (miRNA) are abundant in mammalian milk and may influence the developing gastrointestinal and immune systems of newborn infants. The objectives of this study were to describe the miRNA profile of human breast milk, and to investigate breast milk miRNAs as possible mediators of the observed preventative effect of probiotics.MethodsSmall RNA sequencing was conducted on samples collected 3 months postpartum from 54 women participating in the ProPACT trial. Differential expression of miRNA was assessed for the probiotic vs placebo and AD vs non-AD groups. The results were further analysed using functional prediction techniques.ResultsHuman breast milk samples contain a relatively stable core group of highly expressed miRNAs, including miR-148a-3p, miR-22-3p, miR-30d-5p, let-7b-5p and miR-200a-3p. Functional analysis of these miRNAs revealed enrichment in a broad range of biological processes and molecular functions. Although several miRNAs were found to be differentially expressed on comparison of the probiotic vs placebo and AD vs non-AD groups, none had an acceptable false discovery rate and their biological significance in the development of AD is not immediately apparent from their predicted functional consequences.ConclusionWhilst breast milk miRNAs have the potential to be active in a diverse range of tissues and biological process, individual miRNAs in breast milk 3 months postpartum are unlikely to play a major role in the prevention of atopic dermatitis in infancy by probiotics ingestion in the perinatal period.Trial RegistrationClinicalTrials.gov NCT00159523

BackgroundSevere eczema in young children is associated with an increased risk of developing asthma and rhino-conjunctivitis. In the general population, however, most cases of eczema are mild to moderate. In an unselected cohort, we studied the risk of current asthma and the co-existence of allergy-related diseases at 6 years of age among children with and without eczema at 2 years of age.MethodsQuestionnaires assessing various environmental exposures and health variables were administered at 2 years of age. An identical health questionnaire was completed at 6 years of age. The clinical investigation of a random subsample ascertained eczema diagnoses, and missing data were handled by multiple imputation analyses.ResultsThe estimate for the association between eczema at 2 years and current asthma at 6 years was OR=1.80 (95% CI 1.10-2.96). Four of ten children with eczema at 6 years had the onset of eczema after the age of 2 years, but the co-existence of different allergy-related diseases at 6 years was higher among those with the onset of eczema before 2 years of age.ConclusionsAlthough most cases of eczema in the general population were mild to moderate, early eczema was associated with an increased risk of developing childhood asthma. These findings support the hypothesis of an atopic march in the general population.Trial registrationThe Prevention of Allergy among Children in Trondheim study has been identified as ISRCTN28090297 in the international Current Controlled Trials database