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Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses
Gut microbiota and immune responses
Article first published online: 3 SEP 2009
DOI: 10.1111/j.1365-2222.2009.03326.x
© 2009 Blackwell Publishing Ltd
Additional Information
How to Cite
Sjögren, Y. M., Tomicic, S., Lundberg, A., Böttcher, M. F., Björkstén, B., Sverremark-Ekström, E. and Jenmalm, M. C. (2009), Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clinical & Experimental Allergy, 39: 1842–1851. doi: 10.1111/j.1365-2222.2009.03326.x
Publication History
- Issue published online: 13 NOV 2009
- Article first published online: 3 SEP 2009
- Submitted 29 January 2009; revised 13 May 2009; accepted 12 June 2009
- Abstract
- Article
- References
- Cited By
Keywords:
- Bacteroides fragilis;
- bifidobacteria;
- Clostridium difficile;
- gut microbiota;
- infant;
- lactobacilli;
- SIgA;
- TLR2;
- TLR4
Summary
Introduction Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear.
Objective To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs).
Methods Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex.
Results The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples.
Conclusion Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.