Ola Storrø

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.

Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children

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.

Do early intake of fish and fish oil protect against eczema and doctor-diagnosed asthma at 2 years of age? A cohort study

Background There are ambiguous results regarding the role n-3 polyunsaturated fatty acids and fish might play in primary prevention of allergic diseases. The aim was to investigate the association between cod liver oil and fish consumption during pregnancy and in the first year of life and asthma and eczema at 2 years of age. Methods From the Prevention of Allergy among Children in Trondheim study, a prospective birth cohort study in primary healthcare in Trondheim, Norway, 3086 children were followed prospectively from 1 year to approximately 2 years of age. The primary outcome variable was parental reported asthma and eczema at 2 years. Results The mean age for introducing fish in the diet was 9.1 months. Excluding children with incident eczema before 1 year, a reduced risk of developing eczema was found if the child was eating fish once a week or more, adjusted OR (aOR) for any kind of fish 0.62 (95% CI 0.42 to 0.91 p=0.02), for oily fish aOR 0.21 (95% CI 0.05 to 0.86 p=0.03) and for lean fish aOR 0.67 (95% CI 0.41 to 1.08 p=0.10). The associations between maternal diet and eczema at 2 years and between the dietary factors and doctor-diagnosed asthma were all insignificant. Conclusions 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.

Bifidobacterial Succession and Correlation Networks in a Large Unselected Cohort of Mothers and Their Children

ABSTRACT Bifidobacteria are a major microbial component of infant gut microbiota, which is believed to promote health benefits for the host and stimulate maturation of the immune system. Despite their perceived importance, very little is known about the natural development of and possible correlations between bifidobacteria in human populations. To address this knowledge gap, we analyzed stool samples from a randomly selected healthy cohort of 87 infants and their mothers with >90% of vaginal delivery and nearly 100% breast-feeding at 4 months. Fecal material was sampled during pregnancy, at 3 and 10 days, at 4 months, and at 1 and 2 years after birth. Stool samples were predicted to be rich in the species Bifidobacterium adolescentis, B. bifidum, B. dentium, B. breve, and B. longum. Due to high variation, we did not identify a clear age-related structure at the individual level. Within the population as a whole, however, there were clear age-related successions. Negative correlations between the B. longum group and B. adolescentis were detected in adults and in 1- and 2-year-old children, whereas negative correlations between B. longum and B. breve were characteristic for newborns and 4-month-old infants. The highly structured age-related development of and correlation networks between bifidobacterial species during the first 2 years of life mirrors their different or competing nutritional requirements, which in turn may be associated with specific biological functions in the development of healthy gut.

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.

Temporal Development of the Infant Gut Microbiota in Immunoglobulin E-Sensitized and Nonsensitized Children Determined by the GA-Map Infant Array

ABSTRACT At birth, the human infant gut is sterile, but it becomes fully colonized within a few days. This initial colonization process has a major impact on immune development. Our knowledge about the correlations between aberrant colonization patterns and immunological diseases, however, is limited. The aim of the present work was to develop the GA-map (Genetic Analysis microbiota array platform) infant array and to use this array to compare the temporal development of the gut microbiota in IgE-sensitized and nonsensitized children during the first 2 years of life. The GA-map infant array is composed of highly specific 16S rRNA gene-targeted single nucleotide primer extension (SNuPE) probes, which were designed based on extensive infant 16S rRNA gene sequence libraries. For the clinical screening, we analyzed 216 fecal samples collected from a cohort of 47 infants (16 sensitized and 31 nonsensitized) from 1 day to 2 years of age. The results showed that at a high taxonomic level, Actinobacteria was significantly overrepresented at 4 months while Firmicutes was significantly overrepresented at 1 year for the sensitized children. At a lower taxonomic level, for the sensitized group, we found that Bifidobacterium longum was significantly overrepresented at the age of 1 year and Enterococcus at the age of 4 months. For most phyla, however, there were consistent differences in composition between age groups, irrespective of the sensitization state. The main age patterns were a rapid decrease in staphylococci from 10 days to 4 months and a peak of bifidobacteria and bacteroides at 4 months. In conclusion, our analyses showed consistent microbiota colonization and IgE sensitization patterns that can be important for understanding both normal and diseased immunological development in infants.