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  • 1.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?2009Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

    Delarbeid
    1. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
    Åpne denne publikasjonen i ny fane eller vindu >>Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
    Vise andre…
    2007 (engelsk)Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, nr 5, s. 1174-1180Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Children, eczema, IgE, Lactobacillus, prevention, probiotics, sensitization, skin prick test
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20580 (URN)10.1016/j.jaci.2007.01.007 (DOI)17349686 (PubMedID)
    Tilgjengelig fra: 2009-09-15 Laget: 2009-09-15 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
    Åpne denne publikasjonen i ny fane eller vindu >>Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
    Vise andre…
    2009 (engelsk)Inngår i: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, nr 3, s. 349-354Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Bifidobacteria, Clostridium, Faeces, Probiotics, Lactobacillus reuteri
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20622 (URN)10.1097/MPG.0b013e31818f091b (DOI)19525871 (PubMedID)
    Tilgjengelig fra: 2009-09-15 Laget: 2009-09-15 Sist oppdatert: 2009-09-27bibliografisk kontrollert
    3. Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
    Åpne denne publikasjonen i ny fane eller vindu >>Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
    Vise andre…
    2008 (engelsk)Inngår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, nr 6, s. 497-504Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Lactobacilli, breast milk, TGF-b, sensitization, infancy
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20623 (URN)10.1111/j.1399-3038.2007.00687.x (DOI)18221472 (PubMedID)
    Tilgjengelig fra: 2009-09-15 Laget: 2009-09-15 Sist oppdatert: 2009-09-27bibliografisk kontrollert
    4. A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
    Åpne denne publikasjonen i ny fane eller vindu >>A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
    Vise andre…
    2009 (engelsk)Inngår i: in Allergy, vol 64, 2009, Vol. 64, s. 56-56Konferansepaper, Publicerat paper (Fagfellevurdert)
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-19153 (URN)
    Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2009-09-15bibliografisk kontrollert
  • 2.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Editorial Material: Not all probiotic strains prevent necrotising enterocolitis in premature infants in LANCET, vol 387, issue 10019, pp 624-6252016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, nr 10019, s. 624-625Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 3.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, nr 6, s. 842-850Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 4.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Hedvig E.
    Karolinska Institute, Sweden .
    Andersson, Anders F.
    KTH Royal Institute Technology, Sweden .
    Bjorksten, Bengt
    University of Örebro, Sweden .
    Engstrand, Lars
    KTH Royal Institute Technology, Sweden .
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Reply: Gut microbiota diversity and atopic disease: Does breast-feeding play a role?2013Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, nr 1, s. 248-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    n/a

  • 5.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Hedvig E
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Andersson, Anders F
    Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, Bengt
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and the School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Engstrand, Lars
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Low diversity of the gut microbiota in infants with atopic eczema2012Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, nr 2, s. 434-440Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 6.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Ted
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Oldaeus, Göran
    County Hospital Ryhov, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013Inngår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, nr 6, s. 556-561Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

    Objective

    To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.

    Methods

    A randomized, placebo-controlled trial with oral supplementation with Lreuteri ATCC 55730 (1 × 108 CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.gov ID NCT01285830).

    Results

    The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.

    Conclusion

    The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect of L. reuteri on the immune system seems to be transient. Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

  • 7.
    Abrahamsson, Thomas R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Böttcher, Malin Fagerås
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Oldaeus, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial2007Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, nr 5, s. 1174-1180Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 8.
    Abrahamsson, Thomas R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Sinkiewicz, Gabriela
    Department of Biomedical Lab Science, Malmö University, Malmö, Sweden.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life2009Inngår i: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, nr 3, s. 349-354Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Rautava, Samuli
    University of Turku, Finland; Turku University Hospital, Finland.
    Moore, Aideen M.
    University of Toronto, Canada.
    Neu, Josef
    University of Florida, FL USA.
    Sherman, Philip M.
    University of Toronto, Canada.
    Editorial Material: The Time for a Confirmative Necrotizing Enterocolitis Probiotics Prevention Trial in the Extremely Low Birth Weight Infant in North America Is Now! in JOURNAL OF PEDIATRICS, vol 165, issue 2, pp 389-3942014Inngår i: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 165, nr 2, s. 389-394Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 10.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sandberg, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization2011Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, nr 12, s. 1729-1739Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo. less thanbrgreater than less thanbrgreater thanObjective To relate circulating Th1- and Th2-associated chemokines in infancy to allergic disease, sensitization and probiotic supplementation. less thanbrgreater than less thanbrgreater thanMethods 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. less thanbrgreater than less thanbrgreater thanResults 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. less thanbrgreater than less thanbrgreater thanConclusion 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.

  • 11.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sandberg, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics2009Inngår i: in Allergy, vol 64, 2009, Vol. 64, s. 56-56Konferansepaper (Fagfellevurdert)
    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.

  • 12.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sherman, Philip M.
    University of Toronto, Canada .
    Editorial Material: Multifaceted Effects of Human Milk Oligosaccharides2014Inngår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 209, nr 3, s. 323-324Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 13.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. University of Toronto, Canada.
    You Wu, Richard
    University of Toronto, Canada.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gut microbiota and allergy: the importance of the pregnancy period2015Inngår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, nr 1, s. 214-219Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

  • 14.
    Christmann, Benjamin S.
    et al.
    University of Alabama Birmingham, AL 35294 USA.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Bernstein, Charles N.
    University of Manitoba, Canada.
    Wayne Duck, L.
    University of Alabama Birmingham, AL 35294 USA.
    Mannon, Peter J.
    University of Alabama Birmingham, AL 35294 USA.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Bjorksten, Bengt
    Karolinska Institute, Sweden; University of Örebro, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Elson, Charles O.
    University of Alabama Birmingham, AL 35294 USA.
    Human seroreactivity to gut microbiota antigens2015Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 136, nr 5, s. 1378-1386Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Although immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. Objective: Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response with the response observed in 52 children and their mothers at risk of having allergic disease. Methods: Human serum was collected from adults and children followed from birth to 7 years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed by using a novel protein microarray. Results: Nearly every subject tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. Conclusions: There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic subjects. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota might be needed to prevent certain immune-mediated diseases.

  • 15.
    Connolly, Eamonn
    et al.
    Dept of Research, BioGaia, Stockholm.
    Abrahamsson, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Björkstén, Bengt
    Centrum för Allergiforskning KI, Stockholm.
    Safety of D(-)-lactic acid producing bacteria in the human infant2005Inngår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 41, nr 4, s. 489-492Artikkel i tidsskrift (Fagfellevurdert)
  • 16.
    Fagerås Böttcher, Malin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Abrahamsson, Thomas Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Fredriksson, Mats
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Jakobsson, Ted
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy2008Inngår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, nr 6, s. 497-504Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 17.
    Forsberg, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy2013Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, nr 4, s. 434-442Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 18.
    Forsberg, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Björkstén, Bengt
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.2014Inngår i: Clinical and translational allergy, ISSN 2045-7022, Vol. 4, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Mice 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.

    METHODS: Blood 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.

    RESULTS: Probiotic 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.

    CONCLUSIONS: Decreased 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.

  • 19.
    Jakobsson, Hedvig E
    et al.
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jenmalm, Maria C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Harris, Keith
    School of Engineering, University of Glasgow, Glasgow, UK .
    Quince, Christopher
    School of Engineering, University of Glasgow, Glasgow, UK .
    Jernberg, Cecilia
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden .
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Anders F
    KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Gene Technology, Solna, Sweden.
    Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section2014Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, nr 4, s. 559-566Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 20.
    Stensson, M.
    et al.
    Center of Oral Health, School of Health Sciences, Jönköping.
    Koch, G.
    Department of Pediatric Dentistry, Institute for Postgraduate Dental Education, Jönköping.
    Coric, S.
    Department of Pediatric Dentistry, Institute for Postgraduate Dental Education, Jönköping.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Birkhed, D.
    Department of Cariology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wendt, L.-W.
    Center of Oral Health, School of Health Sciences, Jönköping.
    Oral Administration of Lactobacillus reuteri during the First Year of Life Reduces Caries Prevalence in the Primary Dentition at 9 Years of Age2014Inngår i: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 48, nr 2, s. 111-117Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 21.
    Zamir, Itay
    et al.
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden. Electronic address itay.zamir@umu.se.
    Tornevi, Andreas
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, Umeå University, Umeå, Sweden.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Ahlsson, Fredrik
    Department of Womens and Childrens Health, Uppsala University, Uppsala, Sweden.
    Engström, Eva
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hallberg, Boubou
    CLINTEC Department of Neonatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hansen-Pupp, Ingrid
    Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Pediatrics, Lund, Sweden.
    Sjöström, Elisabeth Stoltz
    Department of Food and Nutrition, Umeå University, Umeå, Sweden.
    Domellöf, Magnus
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Hyperglycemia in Extremely Preterm Infants-Insulin Treatment, Mortality and Nutrient Intakes2018Inngår i: The Journal of Pediatrics, ISSN 0022-3476, Vol. 200, s. 104-110.e1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants.

    Study design

    Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data.

    Results

    Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regressionmodel, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05).

    Conclusions

    Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

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