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Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
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.
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: urn:nbn:se:liu:diva-20626ISBN: 978-91-7393-635-4 (print)OAI: oai:DiVA.org:liu-20626DiVA: diva2:235319
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
List of papers
1. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
Open this publication in new window or tab >>Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
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2007 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, 1174-1180 p.Article in journal (Refereed) Published
Abstract [en]

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 x 10(8) 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.

Keyword
Children, eczema, IgE, Lactobacillus, prevention, probiotics, sensitization, skin prick test
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20580 (URN)10.1016/j.jaci.2007.01.007 (DOI)17349686 (PubMedID)
Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2017-12-13Bibliographically approved
2. Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
Open this publication in new window or tab >>Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
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2009 (English)In: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, no 3, 349-354 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.

MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.

RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.

CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

Keyword
Bifidobacteria, Clostridium, Faeces, Probiotics, Lactobacillus reuteri
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20622 (URN)10.1097/MPG.0b013e31818f091b (DOI)19525871 (PubMedID)
Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2009-09-27Bibliographically approved
3. Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
Open this publication in new window or tab >>Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
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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.

Keyword
Lactobacilli, breast milk, TGF-b, sensitization, infancy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20623 (URN)10.1111/j.1399-3038.2007.00687.x (DOI)18221472 (PubMedID)
Available from: 2009-09-15 Created: 2009-09-15 Last updated: 2009-09-27Bibliographically approved
4. A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
Open this publication in new window or tab >>A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
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2009 (English)In: in Allergy, vol 64, 2009, Vol. 64, 56-56 p.Conference paper, Published paper (Refereed)
Abstract [en]

Background: Analyses of circulating chemokines offer novel tools to investigate the Th1/Th2 imbalance in allergic disease in vivo and explore the influence of pre- and postnatal factors in infancy.

Objective: To relate circulating Th1- and Th2-associated chemokines to the development of allergic disease, pre- and postnatal factors and probiotic supplementation in infancy.

Methods: Circulating levels of Th1-associated CXC-chemokine ligand (CXCL)9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17, CCL18 and CCL22 were assessed with Luminex and ELISA at birth (n=109), 6 (n=104), 12 (n=116) and 24 months (n=123) in 179 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 development of allergic disease and sensitization until two years of age.

Results: The Th2-associated chemokines were as highest at birth and then decreased, whereas the Th1-associated chemokines increased with age. Low Th1- and high Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated CCL22 and reduced CXCL11 levels. High Th2-associated chemokine46 levels were associated with increased birth length and weight and long duration of breastfeeding, and high Th1-associated chemokine levels with day-care attendance. Presence of L. reuteri in stool the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months.

Conclusion: Allergic disease in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels during the first year of life. The chemokine levels were affected by both pre and –postnatal factors.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19153 (URN)
Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-09-15Bibliographically approved

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