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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.

Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more affluent regions. Quantitatively the largest important source of early immune-microbial interaction, the gut microbiota is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the 'dysbiotic drift' in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo controlled trials. In this review, we provide an Accepted ArticleThis article is protected by copyright. All rights reserved.overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high risk infants. It is however stressed that these recommendations are conditional, based on very low quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition.Furthermore, we propose strategies to potentially improve allergy preventive effects and enable future evidence-based implementation.

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Social functions improved through a process of adaptation during the first year after transplantation. Working and travelling were the two most important aspects of social function. All the informants emphasised the importance of regaining a normal life, which was the outcome of a successful adaptation.

BackgroundMice models indicate that intact Toll like receptor (TLR) signaling may be essential for the allergy protective effects of diverse bacterial exposure observed in clinical trials and epidemiological studies. Probiotic supplementation with Lactobacillus reuteri from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at two years (ClinicalTrials.gov NCT01285830). The effect of this supplementation on innate immune responses to bacterial products and the expression of associated TLRs were explored.MethodsBlood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 infants and cultured with TLR2, 4 and 9 ligands. Cytokine and chemokine secretion was determined as well as TLR2, 4 and 9 mRNA expression.ResultsProbiotic supplementation was associated with decreased LTA (lipoteichoic acid) induced CCL4, CXCL8, IL-1β and IL-6 responses at 12 months and decreased CCL4 and IL-1β secretion at 24 months. TLR2 mRNA expression was not affected by probiotic treatment.ConclusionsDecreased responses to TLR2, the main receptor for LTA from Gram positive bacteria, in probiotic treated children seem to be dependent on factors downstream of TLR mRNA expression.

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