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1.  Diversity of the gut microbiota and eczema in early life 
Background
A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results.
Objective
To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture.
Methods
Fecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H') as indicators.
Results
Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32).
Conclusion
Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life.
doi:10.1186/1476-7961-6-11
PMCID: PMC2562383  PMID: 18808715
2.  Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age2 
Background
Low intakes of dietary antioxidants may contribute to increases in asthma and allergy.
Objective
We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children.
Design
Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated, and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year.
Results
No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% CI: 0.48, 1.03] and zinc (OR: 0.59; 95% CI: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% CI: 0.27, 0.90) and zinc (OR: 0.49; 95% CI: 0.27, 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively).
Conclusion
Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.
PMCID: PMC1994925  PMID: 17023719
Asthma; diet; antioxidants; eczema; childhood wheezing
3.  Mode of delivery and cord blood cytokines: a birth cohort study 
Background
The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown.
Objective
To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora).
Methods
CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-γ, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients.
Results
Cesarean section was associated with increased levels of IL-13 and IFN-γ. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P < 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-γ.
Conclusion
Cesarean section is associated with increased levels of IL-13 and IFN-γ, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.
doi:10.1186/1476-7961-4-13
PMCID: PMC1592116  PMID: 17002791
4.  Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression 
Respiratory Research  2006;7(1):40.
Background
Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2), may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy.
Methods
We analyzed immune responses of cord blood mononuclear cells (CBMC) from 50 healthy neonates (31 non-atopic and 19 atopic mothers). Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg) or the allergen house dust mite Dermatophagoides farinae (Derf1), and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR), and the cytotoxic lymphocyte antigen 4 (CTLA4). Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR.
Results
Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07). Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049). IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001), GITR (r = 0.47, p = 0.004) and CTLA4 (r = 0.49, p = 0.003), independent of maternal atopy.
Conclusion
TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to respond to microbial stimuli.
doi:10.1186/1465-9921-7-40
PMCID: PMC1435749  PMID: 16551363

Results 1-4 (4)