Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.

BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season. METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses. RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile). CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.

Perinatal probiotic intervention prevented allergic disease in a Caesarean-delivered subgroup at 13-year follow-up.

BACKGROUND: The long-term effects of probiotic intervention for primary prevention of allergic diseases are not well known. We previously reported less eczema until 10 years in our probiotic intervention trial. OBJECTIVE: To investigate the effect of early probiotic intervention on the prevalence of allergic diseases up to 13 years of age. METHODS: Pregnant women (n = 1223) carrying a child at a high risk of allergy (at least one parent with allergic disease) were randomized to receive a mixture of probiotics (Lactobacillus rhamnosusGG and LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii) or placebo in a double-blind manner from 36 weeks of gestation until birth. Their infants received the same product for the first six months (registration number NCT00298337). At 13-year follow-up, the participants were requested to return a questionnaire and to provide a blood sample. RESULTS: A questionnaire was returned by 642 participants (63.1% of intention-to-treat infants), and 459 provided a blood sample. In the whole cohort, there were no statistically significant differences in doctor-diagnosed allergic disease (55.2% and 59.0%, probiotic and placebo group, respectively) or allergic disease (47.9% and 51.6%) based on the ISAAC questionnaire data. Inhalant-specific IgE sensitization (>0.7 kU/L) was 59.3% in the probiotic group and 49.8% in the placebo group (P = 0.040). In a post hoc analysis made in Caesarean-delivered subgroup, allergy was reported in 41.5% of the probiotic group and 67.9% of the placebo group (P = 0.006), and eczema in 18.9% and 37.5%, respectively (P = 0.031). In the whole cohort, 8.5% of the probiotic group had suffered from wheezing attacks during the previous 12 months vs 14.7% in the placebo group (P = 0.013). There were no statistically significant differences discovered between the characteristics of the participating group and the dropout group. CONCLUSIONS: Probiotic intervention protected Caesarean-delivered subgroup from allergic disease and eczema, but not the total cohort.

Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.

Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).

Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.

Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006-Retrospectively registered, https://clinicaltrials.gov/show/NCT00298337 . The adult-comparison cohort (HELMi) is NCT03996304.