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Feeding Lactobacillus paracasei ssp. paracasei strain F19 to infants during weaning: effects on adaptive immunity and gut microbial function
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: Gut microbial composition has been associated with immune-mediated diseases. Breastfeeding yields a microbiota rich in bifidobacteria and promotes colonization by lactobacilli. Bifidobacteria and lactobacilli are considered health-promoting and are used as probiotics, i.e. live microbial food supplements which when ingested in adequate amounts confer a beneficial effect on the host. During weaning the developing gut immune system is exposed to an increasing variety of antigens from both foods and gut microbiota.

Aims: We aimed to determine if daily feeding of 1x108 colony-forming units (CFU) of the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (LF19) to healthy term infants from 4 to 13 months of age could maintain some of the beneficial effects conferred by breastfeeding on gut microbial composition, with possible effects on gut microbial function, T cell function, Th1/Th2 immune balance and eczema incidence.

Study design: Infants were randomized to daily intake of cereals with (n=89) or without LF19 (n=90) from 4-13 months of age. Clinical outcome measures were monitored by diaries and a questionnaire. Stool and blood samples were obtained at 4, 6½, 9, 13 and 5½, 6½, 12 and 13 months of age, respectively. Stool samples were analyzed for lactobacilli counts by conventional culture methods and the presence of LF19 was verified by randomly amplified polymerase chain reaction (RAPD-PCR). Fecal short-chain fatty acid (SCFA) pattern, a proxy for gut microbial function, was determined by gas-liquid chromatography. After polyclonal or specific activation of T cells, the cytokine mRNA expression levels [interleukin 2 (IL2), IFN-, IL4 and IL10] were determined on isolated mRNA by quantitative real time reverse transcriptase-PCR. Serum concentrations of total and specific IgE antibodies, Haemophilus influenzae type b, diphtheria and tetanus toxoid specific IgG antibodies were analyzed by enzyme immunoassay.

Results: Feeding LF19 maintained high fecal lactobacilli counts during weaning. Persistent colonization with LF19 induced differences in the fecal SCFA pattern. The cumulative incidence of eczema was lower in the probiotic group, in conjunction with a higher IFN-γ/IL4 mRNA ratio in polyclonally activated T cells. Even though there was an effect by LF19 on Th1/Th2 immune balance, there was no effect on IgE sensitization. Infants in both groups increased their capacity to express both Th1 and Th2 cytokines during the second half of infancy but the expression was still lower than that of adults. Infants in the probiotic group had lower IL2 levels after polyclonal T cell activation at 13 months of age compared with infants in the placebo group. Infants fed LF19 did not have fewer infections, but had fewer days with antibiotic prescription compared with infants fed placebo. In addition, compared to placebo, persistent colonization by LF19 enhanced specific vaccine responses to protein antigens during the course of vaccination.

Conclusions: We conclude that feeding LF19 was safe, based on no observed adverse effects in our study. Infants in both groups demonstrated maturation of adaptive immune responses during weaning. Adding probiotics in complementary foods during weaning reduced the risk of eczema by 50%, with a concomitant shift towards an enhanced Th1/Th2 ratio. The reduction of eczema might be explained by probiotic effects on both T cell-mediated immune responses and reinforced gut microbial function.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2008. , 70 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1191
Keyword [en]
adaptive immunity, allergy, complementary food, eczema, gut microbiota, infections, probiotics, short-chain fatty acids, Th1/Th2, weaning
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-1673ISBN: 978-91-7264-585-1 (print)OAI: oai:DiVA.org:umu-1673DiVA: diva2:141793
Public defence
2008-06-05, Sal B, 1D, Tandläkarhögskolan, Norrlands universitetssjukhus, 901 85 Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2008-05-21 Created: 2008-05-21 Last updated: 2013-03-25Bibliographically approved
List of papers
1. Effects of feeding probiotics during weaning on the functional status of gut microbiota in infants
Open this publication in new window or tab >>Effects of feeding probiotics during weaning on the functional status of gut microbiota in infants
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:umu:diva-3264 (URN)
Available from: 2008-05-21 Created: 2008-05-21Bibliographically approved
2. Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines.
Open this publication in new window or tab >>Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines.
Show others...
2008 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 19, no 1, 53-60 p.Article in journal (Other academic) Published
Abstract [en]

Microbial exposure is necessary for the development of normal immune function, which has driven the idea of using probiotics for treatment and prevention of immune-mediated diseases in infancy and childhood. Mounting evidence indicates that probiotics have immunomodulatory effects. However, the mechanisms are still poorly understood. Specific antibody response is a valuable proxy for immune system maturation status in infancy. We aimed at determining the impact of Lactobacillus F19 (LF19) during weaning on infections and IgG antibody responses to routine vaccines. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without LF19 (n = 90) from 4 to 13 months of age. Infants were immunized with DTaP (diphtheria and tetanus toxoid and acellular pertussis), polio and Hib-conjugate vaccines at (3), 5(1/2) and 12 months of age. We assessed the number of days with infections, antibiotic prescriptions and antibody concentrations to Hib capsular polysaccharide (HibPS), diphtheria toxin (D) and tetanus toxoid (T) before and after the second and third doses. Days with infectious symptoms did not differ between the groups. Days with antibiotic prescriptions were fewer in the LF19 group (p = 0.044). LF19 enhanced anti-D concentrations when adjusting for breastfeeding duration and colonization with LF19 (p = 0.024). There was an interaction of the intervention and colonization with LF19 on anti-T concentrations during the course of vaccination (p = 0.035). The anti-HibPS concentrations were higher after the first and second dose of Hib vaccine in infants breastfed <6 months compared with those breastfed > or =6 months (p < 0.05), with no effect by LF19. In conclusion, feeding LF19 did not prevent infections, but increased the capacity to raise immune responses to protein antigens, with more pronounced effects in infants breastfed <6 months.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-8966 (URN)10.1111/j.1399-3038.2007.00583.x (DOI)18086218 (PubMedID)
Available from: 2008-02-22 Created: 2008-02-22 Last updated: 2017-12-14Bibliographically approved
3. Maturation of T cell function in the human infant and effects thereon of probiotic feeding during weaning
Open this publication in new window or tab >>Maturation of T cell function in the human infant and effects thereon of probiotic feeding during weaning
(Esperanto)Manuscript (Other academic)
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-3266 (URN)
Available from: 2008-05-21 Created: 2008-05-21 Last updated: 2015-03-31Bibliographically approved
4. Probiotics during weaning reduce the incidence of eczema.
Open this publication in new window or tab >>Probiotics during weaning reduce the incidence of eczema.
2009 (English)In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 20, 430-7 p.Article in journal (Refereed) Published
Abstract [en]

A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world. Some studies have indicated that probiotics may be effective in the prevention of eczema. In vitro studies indicate that probiotics have immunomodulatory effects. In the present study, we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13 months of age. We assessed the cumulative incidence of eczema at 13 months of age. The ratio of interferon-gamma (IFN-gamma) to interleukin 4 (IL4) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance. Total and specific IgE serum levels were also assessed. The cumulative incidence of eczema at 13 months was 11% (4-17%, 95% CI) and 22% (13-31%, 95% CI) in the probiotic and placebo groups, respectively (p < 0.05). The number needed to treat was 9 (6.5-11.5, 95% CI). At 13 months of age, the IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the placebo group (p < 0.05). In contrast, there were no differences between groups in serum concentrations of IgE. In summary, feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy, e.g., eczema. The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-21698 (URN)10.1111/j.1399-3038.2009.00745.x (DOI)19298231 (PubMedID)
Available from: 2009-04-16 Created: 2009-04-16 Last updated: 2013-04-25

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