Malin Fagerås Böttcher

Altered early infant gut microbiota in children developing allergy up to 5 years of age.

Background Early colonization with bifidobacteria and lactobacilli is postulated to protect children from allergy, while Clostridium (C.) difficile colonization might be associated with allergic disease. Previous studies of infant gut microbiota in relation to subsequent allergy development have mostly employed culture‐dependent techniques, studied genera of bacteria and the follow‐up period was limited to 2 years.

Microflora-associated characteristics in faeces from allergic and nonallergic infants

Background 

Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses

Introduction Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear.

Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy

Maternal intake of omega‐3 (ω‐3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy.

Cytokines in breast milk from allergic and nonallergic mothers.

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-β was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-β, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-β and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-β, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.

Endotoxin levels in Estonian and Swedish house dust and atopy in infancy.

Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1‐stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation.

Leptin and asthma in overweight children at 12 years of age

Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low‐birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin‐associated cytokines might play roles in overweight‐related asthma. Seventy‐four VLBW and 64 normal birth weight (NBW) children participated in a 12‐yr follow up study assessing asthma and allergy. Twenty‐seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)‐γ were analyzed by enzyme‐linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non‐overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non‐overweight children. IFN‐γ was more often detected in the overweight than in the non‐overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN‐γ (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non‐overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2–27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN‐γ might be a pathway in the process of leptin‐induced inflammation.

Chemoattractant factors in breast milk from allergic and nonallergic mothers.

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1α, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.

Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy.

The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast‐fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF‐β1, TGF‐β2, IL‐10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen‐specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF‐β2 and slightly increased levels of IL‐10 in colostrum. For TGF‐β2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF‐β2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE‐associated eczema. The levels of total IgA, SIgA, TGF‐β1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF‐β2, and low levels of this cytokine are associated with less sensitization and possibly less IgE‐associated eczema in breast‐fed infants.

Total and allergen-specific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age.

Background The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned.