Sjögren, Y.M. et al. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin. Exp. Allergy 39, 1842-1851

Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Clinical & Experimental Allergy (Impact Factor: 4.77). 10/2009; 39(12):1842-51. DOI: 10.1111/j.1365-2222.2009.03326.x
Source: PubMed


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.
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).
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.
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-1 beta), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples.
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.

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    • "There are indications that colonization with certain types of microbiota in early life may lead to a decreased responsiveness towards LPS (Sjörgen et al., 2009), i.e., induction of tolerance, and may influence systemic immunity (Da Silva Menezes et al., 2003; Sjörgen et al., 2009 "
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    • "Continued interaction with microbes that live upon and within us represents a most intimate environmental exposure and challenge for the immune system. The microbiota colonizing human gut, skin, and mucosal membranes are integral for energy harvest from food sources (141), metabolism (142, 143), and are implied in the education of the immune system (144, 145). Microbes and microbial communities have been implicated in a variety of diseases that include immune involvement including severe malnutrition (146), obesity (142, 143, 147), chronic obstructive pulmonary disorder (148), and irritable bowl disease (149). "
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    Frontiers in Immunology 09/2014; 5:434. DOI:10.3389/fimmu.2014.00434
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    • "Both cases and controls exhibited higher mean Shannon diversity index scores at higher age groups compared to lower age groups (P <0.001, one-way ANOVA). The diversity of healthy samples positively correlates with age in the first 2 years of life, as previously reported [12]. The diversity index for cases is significantly less than that for controls within each country (P <0.02, Tukey’s t-test corrected for multiple comparisons). "
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