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  • 1.
    Abrahamsson, T. R.
    et al.
    Dept Clin & Expt Med, Div Pediat, Linköping Univ, Linköping, Sweden.
    Jakobsson, H. E.
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Andersson, A. F.
    Sch Biotechnol, Div Gene Technol, Sci Life Lab, Royal Inst Technol (KTH ), Stockholm, Sweden.
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Engstrand, L.
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden; Div Gene Technol, Sci Life Lab, KTH Royal Inst Technol, Sch Biotechnol, Stockholm, Sweden.
    Jenmalm, M. C.
    Dept Clin & Expt Med, Div Pediat, Linköping Univ, Linköping, Sweden; Dept Clin & Expt Med, Div Clin Immunol, Unit Autoimmun & Immune Regulat, Linköping Univ, Linköping, Sweden.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, nr 6, s. 842-850Artikel i tidskrift (Refereegranskat)
    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 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years 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 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). 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 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 2.
    Abrahamsson, Thomas R.
    et al.
    Dept Clin & Expt Med, Div Pediat, Linköping University, Linköping, Sweden.
    Jakobsson, Hedvig E.
    Dept Microbiol Tumor & Cell Biol, Karolinska Institute, Stockholm, Sweden.
    Andersson, Anders F.
    Sch Biotechnol, Sci Life Lab, KTH Royal Inst Technol, Stockholm, Sweden.
    Björksten, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Inst Environm Med, Karolinska Institute, Stockholm, Sweden.
    Engstrand, Lars
    Sch Biotechnol, Sci Life Lab, KTH Royal Inst Technol, Stockholm, Sweden.
    Jenmalm, Maria C.
    Dept Clin & Expt Med, Div Pediat, Linköping University, Linköping, Sweden.; Unit Autoimmun & Immune Regulat, Dept Clin & Expt Med, Div Clin Immunol, Linköping University, Linköping, Sweden.
    Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply2013Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, nr 1, s. 248-249Artikel i tidskrift (Refereegranskat)
  • 3.
    Abrahamsson, Thomas R.
    et al.
    Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden.
    Jakobsson, Hedvig E.
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Anders F.
    Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden .
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; .
    Engstrand, Lars
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Jenmalm, Maria C.
    Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden.
    Low diversity of the gut microbiota in infants with atopic eczema2012Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, nr 2, s. 434-440.e2Artikel i tidskrift (Refereegranskat)
    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.

  • 4. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Ted
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Oldaeus, Göran
    Jenmalm, Maria C.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, nr 6, s. 556-561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Supplementation with the probioticLactobacillus 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 withL.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 withL.reuteriATCC 55730 (1x10(8)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 7yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.govID 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 ofL.reuteri on sensitization andIgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect ofL.reuteri on the immune system seems to be transient. Administration ofL.reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

  • 5.
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Diverse microbial exposure: Consequences for vaccine development2012Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, nr 29, s. 4336-4340Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.

  • 6. Björkstén, Bengt
    Pediatric Allergy Research - are we on the right track?2014Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, nr 1, s. 4-6Artikel i tidskrift (Övrigt vetenskapligt)
  • 7. Forsberg, A.
    et al.
    Abrahamsson, T. R.
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Jenmalm, M. C.
    Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy2013Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, nr 4, s. 434-442Artikel i tidskrift (Refereegranskat)
    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 2years. 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 2years of age.

    Methods: Blood mononuclear cells were collected at birth, 6, 12 and 24months 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 6months (IL-5, P=0.01, and IL-13, P=0.009), with a similar trend for IL-5 at 12months (P=0.09). Cat-induced IFN- responses were also lower after probiotic than after placebo treatment at 24months (P=0.007), with similar findings for the anti-inflammatory IL-10 at birth (P=0.001) and at 12months (P=0.009). At 24months, 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 24months (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.

  • 8.
    Jakobsson, Hedvig E.
    et al.
    Dept Preparedness, Swedish Inst Communicable Dis Control, Solna, Sweden; Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Abrahamsson, Thomas R.
    Div Pediat, Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Jenmalm, Maria C.
    Div Inflammat Med, Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Harris, Keith
    School of Engineering, Univ Glasgow, Glasgow, UK.
    Quince, Christopher
    Sch Engn, Univ Glasgow, Glasgow, UK.
    Jernberg, Cecilia
    Dept Preparedness, Swedish Inst Communicable Dis Control, Solna, Sweden.
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Inst Environm Med, Karolinska Inst, Stockholm, Sweden.
    Engstrand, Lars
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Andersson, Anders F.
    Sci Life Lab, Sch Biotechnol, Div Gene Technol, KTH Royal Inst Technol, Solna, Sweden.
    Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section2014Ingår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, nr 4, s. 559-566Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Östlund-Lagerström, Lina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Kihlgren, Annica
    Örebro universitet, Institutionen för hälsovetenskaper.
    Repsilber, Dirk
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Probiotic administration among free-living older adults: a double blinded, randomised, placebo-controlled clinical trialManuskript (preprint) (Övrigt vetenskapligt)
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