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Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH. (Landstinget i Östergötland)
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
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2008 (English)In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, no 6, 497-504 p.Article in journal (Refereed) Published
Abstract [en]

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-beta1, TGF-beta2, 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-beta2 and slightly increased levels of IL-10 in colostrum. For TGF-beta2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF-beta2 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-beta1, 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-beta2, and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants.

Place, publisher, year, edition, pages
2008. Vol. 19, no 6, 497-504 p.
Keyword [en]
Lactobacilli, breast milk, TGF-b, sensitization, infancy
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-20623DOI: 10.1111/j.1399-3038.2007.00687.xPubMedID: 18221472OAI: oai:DiVA.org:liu-20623DiVA: diva2:235294
Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2009-09-27Bibliographically approved
In thesis
1. Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
Open this publication in new window or tab >>Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.

Aim: The general aim of this thesis was to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.

Subjects: The thesis is based on results obtained from a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease, of whom 188 completed the study.

Methods: The families were recruited at the antenatal clinic, and the mothers received L. reuteri ATCC 55730 (1 x 108 colony forming units) or placebo daily from gestational week 36 until delivery. Their babies then continued with the same study product from birth until 12 months of age and were followed up for another year. The primary outcomes were allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, employing conventional cultivation methods. Cytokines and IgA antibodies were analysed in colostrum and mature milk from the mothers with ELISA, and Na/K- ratio in breast milk with ion selective electrodes. Circulating Th1/Th2-associated chemokines were analysed in cord and peripheral blood in the infants with Luminex or ELISA technique.

Results: The incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L. reuteri group had a lower cumulative incidence of IgE-associated allergic disease, 20% versus 35% (p=0.04), and less IgE-associated eczema during the second year, 8% versus 20% (p=0.02). The prevalence of L. reuteri was higher during the first year of life in stool samples from infants, as well as in colostrum, in the active as compared to the placebo treated group. Colostrum from L. reuteri supplemented mothers had lower levels of TGF-β2, and low levels of this cytokine were associated with less sensitisation. Low Th1- and high Th2-associated chemokine levels preceded allergic disease. The presence of L. reuteri in stool was associated with lower levels of the Th2-associated chemokines CCL17 and CCL22 and higher levels of the Th1-associated CXCL11.

Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the L. reuteri treated infants had lower incidence of IgE-associated allergic disease at two years of age, and therefore possibly run a reduced risk to develop later respiratory allergic disease. The mechanisms underlying this effect require further elucidation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 103 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1126
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20626 (URN)978-91-7393-635-4 (ISBN)
Public defence
2009-10-01, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2012-01-03Bibliographically approved

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Fagerås Böttcher, MalinAbrahamsson, Thomas RobertBjörkstén, Bengt

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