Summary
Background
Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is ...related to allergic disease later in school age.
Objective
To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.
Methods
The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).
Results
Children developing asthma (n = 8) had a lower diversity of the total microbiota than non‐asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE‐associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.
Conclusion and Clinical Relevance
Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.
Summary
Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo.
Objective To relate circulating Th1‐ and ...Th2‐associated chemokines in infancy to allergic disease, sensitization and probiotic supplementation.
Methods Circulating levels of Th1‐associated CXC‐chemokine ligand (CXCL)9, CXCL10 and CXCL11 and Th2‐associated CC‐chemokine ligand (CCL)17 and CCL22 were assessed with Luminex and CCL18 with enzyme‐linked immunosorbent assay at birth (n=109), 6 (n=104), 12 (n=116) and 24 months (n=123) in 161 infants completing a double‐blind placebo‐controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding the development of allergic disease and sensitization until 2 years of age.
Results The Th2‐associated chemokines CCL17 and CCL22 were the highest at birth and then decreased, whereas CCL18 and the Th1‐associated chemokines increased with age. High Th2‐associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated levels of the Th2‐associated CCL22 and reduced levels of the Th1‐associated CXCL11 already at birth. The Th2‐associated CCL17 was also elevated at birth in infants developing recurrent wheeze. A high Th2/Th1 ratio (CCL22/CXCL10) at birth associated with both sensitization and eczema development. The presence of L. reuteri in stool in the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months of age. High Th1‐associated chemokine levels were associated with day‐care.
Conclusion and Clinical Relevance Allergic disease and sensitization in infancy was associated with low circulating Th1‐ and high Th2‐associated chemokine levels already from birth. Circulating chemokines are useful for investigating the Th1/Th2 imbalance in allergic disease in vivo. Elucidation of the role of chemokines in allergic diseases may lead to future treatments (ClinicalTrials.gov NCT01285830).
Cite this as: T. R. Abrahamsson, M. Sandberg Abelius,, A. Forsberg, B. Björkstén and M. C. Jenmalm, Clinical & Experimental Allergy, 2011 (41) 1729–1739.
Background
Allergic diseases have become a major public health problem in affluent societies. Microbial colonization early in life seems to be critical for instructing regulation on immune system ...maturation and allergy development in children. Even though the oral cavity is the first site of encounter between a majority of foreign antigens and the immune system, the influence of oral bacteria on allergy development has not yet been reported.
Objective
We sought to determine the bacterial composition in longitudinally collected saliva samples during childhood in relation to allergy development.
Methods
Illumina sequencing of the 16S rDNA gene was used to characterize the oral bacterial composition in saliva samples collected at 3, 6, 12, 24 months, and 7 years of age from children developing allergic symptoms and sensitization (n = 47) and children staying healthy (n = 33) up to 7 years of age.
Results
Children developing allergic disease, particularly asthma, had lower diversity of salivary bacteria together with highly divergent bacterial composition at 7 years of age, showing a clearly altered oral microbiota in these individuals, likely as a consequence of an impaired immune system during infancy. Moreover, the relative amounts of several bacterial species, including increased abundance of Gemella haemolysans in children developing allergies and Lactobacillus gasseri and L. crispatus in healthy children, were distinctive during early infancy, likely influencing early immune maturation.
Conclusion
Early changes in oral microbial composition seem to influence immune maturation and allergy development. Future experiments should test the probiotic potential of L. gasseri and L. crispatus isolates.
Early changes in oral microbial composition seem to influence immune maturation and allergy development. Oral microbiota increases in bacterial diversity and richness through time. By 7 years of age, allergic children have a lower diversity of salivary bacteria, as well as a highly divergent bacterial composition, compared to healthy children.
Summary
Background
We have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of ...IgE‐associated eczema at 2 years. The underlying immunological mechanisms are unknown, however.
Objective
To investigate the immunomodulatory effect of probiotic supplementation on allergen‐ and mitogen‐induced immune responses in children until 2 years of age.
Methods
Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 children (29 probiotic and 32 placebo treated) and cultured with ovalbumin, birch and cat extract and Phytohaemagglutinin (PHA). Cytokine and chemokine secretion was determined using an in‐house multiplexed Luminex assay and ELISA. Real‐time PCR was performed to investigate the Ebi3, Foxp3, GATA‐3 and T‐bet mRNA expression.
Results
Probiotic treatment was associated with low cat‐induced Th2‐like responses at 6 months (IL‐5, P = 0.01, and IL‐13, P = 0.009), with a similar trend for IL‐5 at 12 months (P = 0.09). Cat‐induced IFN‐γ responses were also lower after probiotic than after placebo treatment at 24 months (P = 0.007), with similar findings for the anti‐inflammatory IL‐10 at birth (P = 0.001) and at 12 months (P = 0.009). At 24 months, Th2‐associated CCL22 levels were lower in the probiotic than in the placebo group after birch stimulation (P = 0.02), with a similar trend after ovalbumin stimulation (P = 0.07). Lower CCL22 levels were recorded at 12 and 24 months (P = 0.03 and P = 0.01) after PHA stimulation.
Conclusion and Clinical Relevance
Lactobacillus reuteri supplementation decreases allergen responsiveness and may enhance immunoregulatory capacity during infancy. L. reuteri supplementation from week 36 and during the first year of life significantly decreases IgE‐associated eczema and lowers allergen and mitogen responsiveness.
Background Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been ...studied. Objective We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development. Methods A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age. Results The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12 months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children. Conclusion An aberrant IgA responsiveness to the gut microbiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.
Objective The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development ...of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.
Background It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing ...incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. Objective We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. Methods Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age ( ClinicalTrials.gov ID NCT01285830 ). Results Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month ( P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month ( P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age ( P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P = .008, q = 0.02). Conclusion Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.
Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio. Prenatal exposures have ...been reported to influence allergy development, possibly induced via changes in maternal immune regulation. In a randomized double-blind placebo-controlled multicenter allergy prevention trial (PROOM-3), pregnant women were recruited at gestational week 20, and randomized to four study groups, one receiving both L. reuteri oil drops and ω-3 PUFA capsules (n = 22), the second receiving ω-3 PUFA supplementation and placebo regarding L. reuteri (n = 21), the third receiving L. reuteri and placebo regarding ω-3 PUFA (n = 22) and the fourth group receiving placebo capsules and placebo oil drops (n = 23). In this substudy, supplemental and pregnancy-related effects on maternal peripheral immune cell populations during pregnancy were assessed by flow cytometry immune phenotyping at gestational week 20, 32 and 4 days after delivery. The numbers of activated and regulatory T (Treg) cells (CD45RA
Foxp3
/CD45RA
Foxp3
) were reduced after delivery, with the lowest count in the L. reuteri supplemented group compared with the placebo group 4 days after delivery, while the ω-3 PUFA group did not differ from the placebo group. Several treatment-independent changes were observed during and after pregnancy in lymphocytes (CD4
/8
/19
/56
/45RA
), CD14
16
monocytes, and in subpopulations of T helper cells (Th) CD4
CD45RA
Tbet
(Th1) and CD4
CD45RA
RORC
(Th17) cells. In conclusion, probiotic supplementation to the mother during the second half of pregnancy resulted in immunomodulatory effects among activated and resting Treg cells. Furthermore, several systemic immune modifying effects of pregnancy were observed.
The aim of this study was to evaluate the effect on oral health, at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730, to mothers during the last ...month of gestation and to children through the first year of life. The study was a single-blind, placebo-controlled, multicenter trial involving 113 children: 60 in the probiotic and 53 in the placebo group. The subjects underwent clinical and radiographic examination of the primary dentition and carious lesions, plaque and gingivitis were recorded. Saliva and plaque were sampled for determination of mutans streptococci (MS) and lactobacilli (LB) in saliva and plaque as well as salivary secretory IgA (SIgA). Forty-nine (82%) children in the probiotic group and 31 (58%) in the placebo group were caries-free (p < 0.01). The prevalence of approximal caries lesions was lower in the probiotic group (0.67 ± 1.61 vs. 1.53 ± 2.64; p < 0.05) and there were fewer sites with gingivitis compared to the placebo group (p < 0.05). There were no significant differences between the groups with respect to frequency of toothbrushing, plaque and dietary habits, but to intake of fluoride supplements (p < 0.05). There were no intergroup differences with respect to L. reuteri, MS, LB or SIgA in saliva. Within the limitation of this study it seems that daily supplementation with L. reuteri from birth and during the first year of life is associated with reduced caries prevalence and gingivitis score in the primary dentition at 9 years of age.
Background An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. Objective To prevent eczema ...and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. Methods Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 × 108 colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Results The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% ( P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% ( P = .02). Wheeze and other potentially allergic diseases were not affected. Conclusion Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. Clinical implication Probiotics may reduce the incidence of IgE-associated eczema in infancy.
PDF
