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Björkstén, Bengt
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Publications (9 of 9) Show all publications
Jakobsson, H. E., Abrahamsson, T. R., Jenmalm, M. C., Harris, K., Quince, C., Jernberg, C., . . . Andersson, A. F. (2014). Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section. Gut, 63(4), 559-566
Open this publication in new window or tab >>Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section
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2014 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 4, p. 559-566Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
London: BMJ Publishing Group, 2014
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-35355 (URN)10.1136/gutjnl-2012-303249 (DOI)000332267500006 ()
Funder
Swedish Research CouncilSwedish Research Council Formas
Note

Funding Agencies:

Ekhaga Foundation and the Soderbergs Foundation

Research Council for the South-East Sweden

Swedish Asthma and Allergy Association

Olle Engkvist Foundation

Vardal Foundation-for Health Care Sciences and Allergy Research

Swedish Research Councils VR

Unilever

Available from: 2014-06-13 Created: 2014-06-13 Last updated: 2018-09-06Bibliographically approved
Abrahamsson, T. R., Jakobsson, H. E., Andersson, A. F., Björkstén, B., Engstrand, L. & Jenmalm, M. C. (2014). Low gut microbiota diversity in early infancy precedes asthma at school age. Clinical and Experimental Allergy, 44(6), 842-850
Open this publication in new window or tab >>Low gut microbiota diversity in early infancy precedes asthma at school age
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2014 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed) Published
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.

Keywords
asthma, allergic rhinoconjunctivitis, birth, children, diversity, hygiene hypothesis, microbiota, molecular microbiology
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-35822 (URN)10.1111/cea.12253 (DOI)000337529100006 ()
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding Agency:

BioGaia AB, Stockholm, Sweden

Ekhaga Foundation

Research Council for the South-East Sweden

Olle Engkvist Foundation

Swedish Asthma and Allergy Association

University Hospital of Linkoping

Soderberg Foundation

Vardal Foundation for Health Care Science and Allergy Research, Sweden

Available from: 2014-08-27 Created: 2014-07-30 Last updated: 2018-08-28Bibliographically approved
Björkstén, B. (2014). Pediatric Allergy Research - are we on the right track?. Pediatric Allergy and Immunology, 25(1), 4-6
Open this publication in new window or tab >>Pediatric Allergy Research - are we on the right track?
2014 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 1, p. 4-6Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Hoboken: Wiley-Blackwell, 2014
Keywords
Eczema; Childhood; Asthma; Rhinoconjunctivitis; Prevalence; Probiotics; Symptons; Children; Infancy; Breast
National Category
Medical and Health Sciences
Research subject
Medicine; Immunology; Pediatrics
Identifiers
urn:nbn:se:oru:diva-34858 (URN)10.1111/pai.12184 (DOI)000331469300002 ()
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2017-12-05Bibliographically approved
Abrahamsson, T. R., Jakobsson, H. E., Andersson, A. F., Björksten, B., Engstrand, L. & Jenmalm, M. C. (2013). Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply [Letter to the editor]. Journal of Allergy and Clinical Immunology, 131(1), 248-249
Open this publication in new window or tab >>Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply
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2013 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, p. 248-249Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Mosby-Elsevier, 2013
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:oru:diva-54889 (URN)10.1016/j.jaci.2012.10.045 (DOI)000312961200047 ()23199606 (PubMedID)
Available from: 2017-01-23 Created: 2017-01-23 Last updated: 2020-01-23Bibliographically approved
Abrahamsson, T. R., Jakobsson, T., Björkstén, B., Oldaeus, G. & Jenmalm, M. C. (2013). No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy. Pediatric Allergy and Immunology, 24(6), 556-561
Open this publication in new window or tab >>No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy
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2013 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 6, p. 556-561Article in journal (Refereed) Published
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.

Keywords
allergic rhinoconjunctivitis, asthma, children, eczema, fractional exhaled nitric oxide, prevention, probiotics, randomized, sensitization, skin prick test
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-30900 (URN)10.1111/pai.12104 (DOI)000323645500007 ()
Available from: 2013-09-26 Created: 2013-09-20 Last updated: 2017-12-06Bibliographically approved
Forsberg, A., Abrahamsson, T. R., Björkstén, B. & Jenmalm, M. C. (2013). Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy. Clinical and Experimental Allergy, 43(4), 434-442
Open this publication in new window or tab >>Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy
2013 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, no 4, p. 434-442Article in journal (Refereed) Published
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.

Keywords
allergen, allergy, chemokine, cytokine, eczema, Foxp3, infancy, Lactobacillus reuteri, probiotics, sensitization
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-28901 (URN)10.1111/cea.12082 (DOI)000316623800008 ()
Available from: 2013-05-06 Created: 2013-05-03 Last updated: 2017-12-06Bibliographically approved
Björkstén, B. (2012). Diverse microbial exposure: Consequences for vaccine development. Vaccine, 30(29), 4336-4340
Open this publication in new window or tab >>Diverse microbial exposure: Consequences for vaccine development
2012 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 29, p. 4336-4340Article, review/survey (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxon, United Kingdom: Elsevier, 2012
Keywords
Microbiota, probiotics, immune regulation, vaccines, adjuvant
National Category
Medical and Health Sciences Immunology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-25002 (URN)10.1016/j.vaccine.2011.10.074 (DOI)000306299200008 ()22079075 (PubMedID)2-s2.0-84861962385 (Scopus ID)
Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2018-05-09Bibliographically approved
Abrahamsson, T. R., Jakobsson, H. E., Andersson, A. F., Björkstén, B., Engstrand, L. & Jenmalm, M. C. (2012). Low diversity of the gut microbiota in infants with atopic eczema. Journal of Allergy and Clinical Immunology, 129(2), 434-440.e2
Open this publication in new window or tab >>Low diversity of the gut microbiota in infants with atopic eczema
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2012 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 2, p. 434-440.e2Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
New York, USA: Elsevier, 2012
Keywords
Allergic disease, Bacteroides species, diversity, eczema, hygiene hypothesis, infant, microbiota, molecular microbiology, pyrosequencing, Sutterella species
National Category
Medical and Health Sciences Pediatrics
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22127 (URN)10.1016/j.jaci.2011.10.025 (DOI)000299951700021 ()22153774 (PubMedID)2-s2.0-84856454758 (Scopus ID)
Note

Funding Agencies:

BioGaia AB, Stockholm, Sweden 

Ekhaga Foundation, the Heart and Lung foundation 

Research Council for the South-East Sweden 

Olle Engqvist Foundation 

Swedish Asthma and Allergy Association

Swedish Research Council 

University Hospital of Linköping 

Söderberg Foundation 

Vardal Foundation for Health Care Science and Allergy Research, Sweden 

BioGaia AB 

Available from: 2012-03-16 Created: 2012-03-16 Last updated: 2017-12-07Bibliographically approved
Östlund-Lagerström, L., Kihlgren, A., Repsilber, D., Björkstén, B., Brummer, R. J. & Schoultz, I.Probiotic administration among free-living older adults: a double blinded, randomised, placebo-controlled clinical trial.
Open this publication in new window or tab >>Probiotic administration among free-living older adults: a double blinded, randomised, placebo-controlled clinical trial
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-49597 (URN)
Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2018-01-10Bibliographically approved
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