Background: Early colonization with bifidobacteria and lactobacilli is postulated to protect

Summary 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. Objective To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll‐like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)‐induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs). Methods Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real‐time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real‐time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex. Results The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS‐induced production of inflammatory cytokines and chemokines, e.g. IL‐6 and CCL4 (MIP‐1β), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples. Conclusion Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down‐regulate LPS responsiveness in infancy.

BackgroundMicrobial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age.Methods and FindingsFecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, Clostridium (C.) difficile, a group of Lactobacilli (Lactobacillus (L.) casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014). However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028). Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038). Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048).ConclusionIn this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that early Lactobacilli (L. casei, L. paracasei, L. rhamnosus) colonization seems to decrease the risk for allergy at five years of age despite allergic heredity.

Several recent studies have demonstrated a relationship between the composition of the gut microbiota in infancy and subsequent development of allergic disease. Human milk is the major food in infancy and may thus profoundly influence the composition of the gut flora. Oligosaccharides in breast milk survive the passage through the stomach and are utilized by the gut microbiota. As the relationship between breast feeding and childhood allergy is controversial we hypothesized that the composition of oligosaccharides in breast milk might explain the controversy. Nine of the most abundant neutral oligosaccharides in human milk were analysed in colostrum samples from allergic and non-allergic women and related to subsequent development of allergy in their children. The carbohydrate fraction of the colostrum was separated by gel permeation chromatography and neutral oligosaccharides, tri- to hexasaccharides were collected. Neutral oligosaccharides were analysed with high-performance liquid chromatography. There was a large variation in the concentration of neutral oligosaccharides in colostrum, which could not be explained by the allergic status of the women. Allergic children consumed higher amounts of neutral oligosaccharides in total, although not significantly (p = 0.12). When different oligosaccharides were analysed separately, there was no significant difference in consumption between the infants who developed atopic allergy later (n = 9) and infants who did not (n = 11). Thus, the amount of neutral oligosaccharides in colostrum does not directly correlate with maternal allergy, nor with allergy development in children up to 18 months of age.