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Forsberg, Anna
Publikasjoner (8 av 8) Visa alla publikasjoner
Forsberg, A. (2017). Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Åpne denne publikasjonen i ny fane eller vindu >>Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies
2017 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The incidence of allergic diseases is increasing, possibly due to a reduced intensity and diversity of microbial stimulation. More knowledge is needed on the immunological mechanisms underlying the eczema preventive effect of pre- and postnatal probiotic supplementation. The pregnancy period seems to be of essential importance, since both epidemiological and experimental animal studies show the importance of microbial exposure during gestation on allergy prevention.

We have performed a study where the probiotic lactic acid producing bacteria Lactobacillus reuteri was supplemented to pregnant women, at risk of having an allergic infant. The pregnant mothers received the study product from gestational week 36 until delivery, and the infants then continued with the same product until one year of age. The probiotic, as compared with placebo, supplemented infants had less IgE-associated eczema at two years of age.

In order to investigate how the supplementation affected the immune system peripheral blood was collected and immune cells were stimulated with common allergens and TLR ligands. The probiotic treated group responded with a more regulated response to allergens and TLR2 ligands in comparison to the placebo supplemented group. We also investigated how the probiotic supplementation affected the epigenetic methylation pattern in circulating T helper cells during infancy, observing the most pronounced effects at birth.

In a follow up study, supplementation was started earlier to possibly gain a stronger allergy preventive effect via changes in maternal immune regulation. Supplementation with Lactobacillus reuteri and ω-3 fatty acids started at gestational week 20 and throughout pregnancy. After 20 weeks of supplementation, some immunomodulatory effects among circulating activated regulatory T cells and a subpopulation of monocytes were noted. Several systemic immune modifying effects of pregnancy were observed.

In summary, probiotics show several immunomodulatory effects in infants and pregnant women. However, more research is needed to better understand the effects of the probiotic supplementation to aid future identification of more efficacious allergy preventive strategies.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2017. s. 107
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1589
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-142332 (URN)10.3384/diss.diva-142332 (DOI)9789176854433 (ISBN)
Disputas
2017-11-17, Hasselquistsalen, Campus US, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2017-10-26 Laget: 2017-10-26 Sist oppdatert: 2019-10-28bibliografisk kontrollert
Forsberg, A., Bengtsson, M., Eringfält, A., Ernerudh, J., Mjösberg, J. & Jenmalm, M. (2014). Letter: GATA binding protein 3(+) group 2 innate lymphoid cells are present in cord blood and in higher proportions in male than in female neonates. [Letter to the editor]. Journal of Allergy and Clinical Immunology, 134(1), 228-230
Åpne denne publikasjonen i ny fane eller vindu >>Letter: GATA binding protein 3(+) group 2 innate lymphoid cells are present in cord blood and in higher proportions in male than in female neonates.
Vise andre…
2014 (engelsk)Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 134, nr 1, s. 228-230Artikkel i tidsskrift, Letter (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
Elsevier, 2014
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-108375 (URN)10.1016/j.jaci.2014.01.027 (DOI)000338930300032 ()24636083 (PubMedID)
Merknad

n/a

Tilgjengelig fra: 2014-06-27 Laget: 2014-06-27 Sist oppdatert: 2017-12-05
Forsberg, A., Abrahamsson, T., Björkstén, B. & Jenmalm, M. (2014). Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.. Clinical and translational allergy, 4, 1-7
Åpne denne publikasjonen i ny fane eller vindu >>Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.
2014 (engelsk)Inngår i: Clinical and translational allergy, ISSN 2045-7022, Vol. 4, s. 1-7Artikkel i tidsskrift (Fagfellevurdert) Published
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.

Emneord
Angina pectoris; Coronary ostial stenosis; Takayasu
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-111347 (URN)10.1186/2045-7022-4-21 (DOI)25002964 (PubMedID)
Tilgjengelig fra: 2014-11-18 Laget: 2014-10-15 Sist oppdatert: 2017-10-26
Forsberg, A., Abrahamsson, T., Björksten, B. & Jenmalm, M. (2013). Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy. Clinical and Experimental Allergy, 43(4), 434-442
Åpne denne publikasjonen i ny fane eller vindu >>Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy
2013 (engelsk)Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, nr 4, s. 434-442Artikkel i tidsskrift (Fagfellevurdert) 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 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.

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2013
Emneord
allergen, allergy, chemokine, cytokine, eczema, Foxp3, infancy, Lactobacillus reuteri, probiotics, sensitization
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-91537 (URN)10.1111/cea.12082 (DOI)000316623800008 ()
Merknad

Funding Agencies|Swedish Research Council|K2011-56X-21854-01-06|Ekhaga Foundation||Olle Engkvist Foundation||Heart and Lung foundation||Research Council for the South-East Sweden|F2000-106|Swedish Asthma and Allergy Association||Cancer and Allergy Association||BioGaia AB, Stockholm, Sweden||University Hospital of Linkoping, Sweden||

Tilgjengelig fra: 2013-04-26 Laget: 2013-04-26 Sist oppdatert: 2017-12-06
Abrahamsson, T., Sandberg, M., Forsberg, A., Bjorksten, B. & Jenmalm, M. (2011). A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization. Clinical and Experimental Allergy, 41(12), 1729-1739
Åpne denne publikasjonen i ny fane eller vindu >>A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization
Vise andre…
2011 (engelsk)Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, nr 12, s. 1729-1739Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
Blackwell Publishing, 2011
Emneord
chemokine, day-care, eczema, infant, Lactobacillus reuteri, pregnancy, probiotics, sensitization, skin prick test, Wheeze
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-73095 (URN)10.1111/j.1365-2222.2011.03827.x (DOI)000297283800009 ()
Merknad
Funding Agencies|BioGaia AB, Stockholm, Sweden||Ekhaga Foundation||Heart and Lung foundation||Research Council for the South-East Sweden|F2000-106|Swedish Asthma and Allergy Association||Swedish Research Council||University Hospital of Linkoping, Sweden||Tilgjengelig fra: 2011-12-16 Laget: 2011-12-16 Sist oppdatert: 2017-12-08
Forsberg, A., Straka, E., Johansson, E., Mehta, R., Berg, G., Jenmalm, M. C., . . . Ernerudh, J. (2011). Plasticity and flexibility of T cells in human pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 149-149. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 149-149). Elsevier, 90(2)
Åpne denne publikasjonen i ny fane eller vindu >>Plasticity and flexibility of T cells in human pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 149-149
Vise andre…
2011 (engelsk)Inngår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, nr 2, s. 149-149Konferansepaper, Publicerat paper (Fagfellevurdert)
Abstract [en]

Introduction:Pregnancy challenges the immune system. Thus, tolerance to the semi-allogenic fetus must be supported while the mother and fetus still must be protected against infectious agents. Pregnancy is associated with a Th2 deviated immune system, away from a harmful Th1 associated immunity, although this may be a simplified view. Regulatory T cells (Tregs) are enriched in the uterus, but occur at normal frequency in the circulation. It has become increasingly evident that Tregs and T helper cells are not stably committed lineages but are plastic, showing close relationships between subsets. We hypothesize that an increased T cell flexibility in pregnancy can help to explain the paradox of simultaneous tolerance and strong antimicrobial responses. Our aim was to investigate whether the plasticity concept is applicable for the Treg subset, and if it involves the entire T helper population.

Material and methods: Isolated Tregs (CD4dimCD25high) and control cells (CD4+CD25−) from second trimester pregnant (n = 14) and non-pregnant women (n = 14) were stimulated for 24 h with plate-bound anti-CD3/anti-CD28. Signature gene and protein expression of each T cell subset was measured using transcription factor expression by real time-PCR and multiplex bead array of cell culture supernatants, respectively. The whole PBMC fraction is also used in ongoing experiments and either stimulated with plate-bound anti-CD3/anti-CD28 or with the Th1, Th2 and Th17 deviating microbial agents PPD (Th1), TT (Th2) and C. albicans hyphae (Th17). After culturing, the cells are stained for intracellular transcription factors associated with Th1, Th2, Th17 and Treg immunity.

Results: Stimulated Tregs from pregnant compared to non-pregnant women showed significantly higher levels of markers for Treg cells (Foxp3 mRNA), Th2 cells (GATA-3 mRNA and IL4 protein) and a tendency to increase in markers of Th17 (RORC mRNA and IL-17 protein), whereas Th1 markers (Tbet mRNA and IFN-γ) showed no difference between pregnant and non-pregnant women. Further, ongoing studies may reveal if the entire T helper population shows a higher degree of responsiveness during pregnancy.

Conclusions: Our results imply an increased plasticity of the Treg population during pregnancy, suggesting that Treg cells are able to switch to a Th2/Th17-like phenotype, depending on current demands of tolerance or infectious threats.

sted, utgiver, år, opplag, sider
Elsevier, 2011
Emneord
Pregnancy, T cell plasticity, Tolerance, Infectious agents
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-70335 (URN)10.1016/j.jri.2011.06.034 (DOI)000293873500032 ()
Tilgjengelig fra: 2011-09-02 Laget: 2011-09-02 Sist oppdatert: 2011-09-06
Ernerudh, J., Forsberg, A., Straka, E., Johansson, E., Bhai Mehta, R., Svensson, J., . . . Jenmalm, M. (2011). T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-131. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 131-131). Elsevier, 90(2)
Åpne denne publikasjonen i ny fane eller vindu >>T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-131
Vise andre…
2011 (engelsk)Inngår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, nr 2, s. 131-131Konferansepaper, Publicerat paper (Fagfellevurdert)
Abstract [en]

n/a

sted, utgiver, år, opplag, sider
Elsevier, 2011
Emneord
Pregnancy, T helper cell, Tolerance
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-70334 (URN)10.1016/j.jri.2011.06.003 (DOI)000293873500002 ()
Tilgjengelig fra: 2011-09-02 Laget: 2011-09-02 Sist oppdatert: 2012-03-25
Abrahamsson, T., Sandberg, M., Forsberg, A., Bjorksten, B. & Jenmalm, M. (2009). A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics. In: in Allergy, vol 64 (pp. 56-56). , 64
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
Organisasjoner