The development of childhood atopy is postulated to be influenced by perinatal microbial exposure. Inadequate numbers of probiotic organisms forming the intestinal microbiota, is an early pre-symptomatic feature linked to the expression of allergy. Perinatal probiotic supplementation is therefore hypothesized to contribute to the microbiota mediated immunomodulatory response determining immune hypo- responsiveness to allergens. Aims: This thesis examined the anti-allergy immunomodulatory effects of probiotic bacteria invitro in the context of the pathophysiology of atopy, as a preamble to perinatal probiotic supplementation. Methods: Cytokine responses were measured after umbilical cord blood mononuclear cells (CBMCs) were co-cultured in the presence of a consortium of probiotic organisms consisting of two strains of lactobacilli and two strains of bifidobacteria. Additionally pregnant women with a familial history of allergic disease from 36 weeks gestation and their infants to age 6 months, were supplemented with probiotics or a placebo daily. The immunomodulatory effects of probiotics on immune function in vivo was then analysed within the peripheral blood of the supplemented neonates. Results: CBMCs co-cultured in the presence of the probiotic consortium generated a dose dependent, monocyte mediated release of the pro-inflammatory cytokines TNF-a, IL- 12p70, IFN-y and the immunosuppressive cytokines IL-10 and TGF-pi. The consortium down regulated PH A and SEB induced IL-13 (a key allergy orchestrating cytokine) while potentiating IFN-y (a key Thl driving cytokine) responses from CBMCs. Interestingly in the probiotic supplemented group the cord blood eosinophil count was significantly reduced. Additionally the IL-12p70 concentrations in microbial stimulated venous blood at age 6 months was significantly elevated in comparison to the placebo supplemented group. Conclusion: The immunomodulatory effect of probiotic bacteria is marked by a capacity to promote a Thl orientation of the immune system. Probiotics administered during pregnancy and early infancy may therefore be effective in the prevention of Th2 mediated atopic disorder.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:678385 |
| Date | January 2015 |
| Creators | Omakobia, Michael |
| Publisher | Swansea University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://cronfa.swan.ac.uk/Record/cronfa42897 |
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