Christian Kvikne Dotterud

Probiotics in pregnant women to prevent allergic disease: a randomized, double-blind trial

Background  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.

Temporal variations in early gut microbial colonization are associated with allergen-specific immunoglobulin E but not atopic eczema at 2 years of age.

Background Intestinal microbiota undergoes substantial development during the first 2 years of life, important for intestinal immunologic development and maturation influencing systemic immune responses.

Early eczema and the risk of childhood asthma: a prospective, population-based study

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

Does Maternal Perinatal Probiotic Supplementation Alter the Intestinal Microbiota of Mother and Child

Objectives: Maternal probiotic supplementation has been shown to prevent the development of atopic dermatitis in the offspring. We aimed to investigate whether probiotics in pregnant and breast-feeding mothers altered the colonization pattern and the diversity of the mothers’ and childrens intestinal microbiota. Methods: In a randomized, double-blind trial, women received probiotic milk or placebo from 36 weeks of gestation up to 3 months postnatally while breast-feeding. The probiotic milk contained Lactobacillus rhamnosus GG, L acidophilus La-5, and Bifidobacterium animalis subsp. lactis Bb-12. Stool samples were collected from the mothers at 30 to 36 weeks of gestation and 3 months after birth, and from the child at age 10 days, 3 months, 1 year, and 2 years, and bacteria were analyzed by quantitative polymerase chain reaction. Additionally, stool samples from 3-month-old and 2-year-old children were characterized using 16S ribosomal RNA gene deep sequencing to estimate the bacterial classes and genera, and the &agr;- and &bgr;-diversity. Results: Three months after birth, both the prevalence and the relative abundance of the administered probiotic bacteria were significantly increased among the mothers in the probiotic group compared with among those in the placebo group. Only the Lactobacillus rhamnosus GG bacteria colonized the children at 10 days and at 3 months of age. There were no significant differences in the abundance of the administered probiotic bacteria between the groups at 1 and 2 years of age. For the bacterial classes and genera, and &agr;- and &bgr;-diversity, there were no significant differences between the groups. Conclusions: 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 &agr;- and &bgr;-diversity of the children.

Transition from infant- to adult-like gut microbiota

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.

The impact of pre- and postnatal exposures on allergy related diseases in childhood: a controlled multicentre intervention study in primary health care.

BackgroundEnvironmental factors such as tobacco exposure, indoor climate and diet are known to be involved in the development of allergy related diseases. The aim was to determine the impact of altered exposure to these factors during pregnancy and infancy on the incidence of allergy related diseases at 2 years of age.MethodsChildren from a non-selected population of mothers were recruited to a controlled, multicenter intervention study in primary health care. The interventions were an increased maternal and infant intake of n-3 PUFAs and oily fish, reduced parental smoking, and reduced indoor dampness during pregnancy and the children’s first 2 years of life. Questionnaires on baseline data and exposures, and health were collected at 2 years of age.ResultsThe prevalence of smoking amongst the mothers and fathers was approximately halved at 2 years of age in the intervention cohort compared to the control cohort. The intake of n-3 PUFA supplement and oily fish among the children in the intervention cohort was increased. There was no significant change for indoor dampness. The odds ratio for the incidence of asthma was 0.72 (95% CI, 0.55-0.93; NNTb 53), and 0.75 for the use of asthma medication (95% CI, 0.58-0.96). The odds ratio for asthma among girls was 0.41 (95% CI 0.24-0.70; NNTb 32), and for boys 0.93 (95% CI 0.68-1.26). There were no significant change for wheeze and atopic dermatitis.ConclusionReduced tobacco exposure and increased intake of oily fish during pregnancy and early childhood may be effective in reducing the incidence of asthma at 2 years of age. The differential impact in boys and girls indicates that the pathophysiology of asthma may depend on the sex of the children.Trial registrationCurrent Controlled Trials ISRCTN28090297.

High-Resolution Analyses of Overlap in the Microbiota Between Mothers and Their Children

Abstract Understanding the transmission of the human microbiota from mother to child is of major importance. Although we are gaining knowledge using 16S rRNA gene analyses, the resolution of this gene is not sufficient to determine transmission patterns. We therefore developed an Illumina deep sequencing approach targeting the 16–23S rRNA Internal Transcribed Spacer (ITS) for high-resolution microbiota analyses. Using this approach, we analyzed the composition and potential mother to child transmission patterns of the microbiota (milk and stool) in a longitudinal cohort of 20 mother/child pairs. Our results show overlap in the infant stool microbiota with both mother’s milk and stool, and that the overlap with stool increases with age. We found an Operational Taxonomic Unit resembling Streptococcus gordonii as the most widespread colonizer of both mothers and their children. In conclusion, the increased resolution of 16–23S rRNA ITS deep sequencing revealed new knowledge about potential transmission patterns of human-associated bacteria.