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Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. , 107 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1589
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:liu:diva-142332DOI: 10.3384/diss.diva-142332ISBN: 9789176854433 (print)OAI: oai:DiVA.org:liu-142332DiVA: diva2:1152784
Public defence
2017-11-17, Hasselquistsalen, Campus US, 09:00 (English)
Opponent
Supervisors
Available from: 2017-10-26 Created: 2017-10-26 Last updated: 2017-10-26Bibliographically approved
List of papers
1. Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy
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, 434-442 p.Article 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 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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keyword
allergen, allergy, chemokine, cytokine, eczema, Foxp3, infancy, Lactobacillus reuteri, probiotics, sensitization
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91537 (URN)10.1111/cea.12082 (DOI)000316623800008 ()
Note

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||

Available from: 2013-04-26 Created: 2013-04-26 Last updated: 2017-10-26
2. Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.
Open this publication in new window or tab >>Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.
2014 (English)In: Clinical and translational allergy, ISSN 2045-7022, Vol. 4, 1-7 p.Article in journal (Refereed) 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.

Keyword
Angina pectoris; Coronary ostial stenosis; Takayasu
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-111347 (URN)10.1186/2045-7022-4-21 (DOI)25002964 (PubMedID)
Available from: 2014-11-18 Created: 2014-10-15 Last updated: 2017-10-26

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