Abstract
Microbial exposure early in life influences immune maturation and potentially also the development of immune-mediated disease. Here we studied early-life gut colonization in relation to cytokine responses at two years of age. Fecal samples were collected from infants during the first two months of life. DNA was extracted from the fecal samples and Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, a group of lactobacilli (L. casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus were detected with real time PCR. Peripheral mononuclear cells were stimulated with phytohaemagglutinin (PHA) and numbers of IL-4−, IL-10− and IFN-γ secreting cells were evaluated using ELISpot. We further stimulated peripheral blood mononuclear cells with bacterial supernatants in vitro and assessed the IL-4−, IL-10− and IFN-γ inducing capacity by flow cytometry and ELISA. Early S. aureus colonization associated with higher numbers of IL-4− (p = 0.022) and IL-10 (p = 0.016) producing cells at two years of age. In contrast to colonization with S. aureus alone, co-colonization with lactobacilli associated with suppression of IL-4− (p = 0.004), IL-10− (p = 0.004) and IFN-γ (p = 0.034) secreting cells. In vitro stimulations of mononuclear cells with bacterial supernatants supported a suppressive role of L. rhamnosus GG on S. aureus-induced cytokine responses. We demonstrate that the early gut colonization pattern associates with the PHA-induced cytokine profile at two years of age and our in vitro findings support that specific bacterial species influence the T helper cell subsets. This suggests that dysbiosis in the early microbiota may modulate the risk of developing inflammatory conditions like allergy.
Highlights
The gut microbiota performs necessary metabolic functions such as production of short chain fatty acids and synthesis of vitamins
The bifidobacteria frequencies remained stable throughout the two months, except B. bifidum frequency, which increased to 53,4% at the age of two months
Based on the hypothesis that the early-life gut microbiota composition influences infant immune maturation, we have investigated early gut bacterial species in relation to numbers of cytokine-secreting cells at two years of age
Summary
The gut microbiota performs necessary metabolic functions such as production of short chain fatty acids and synthesis of vitamins. It influences the maturation of the immune system after birth, which is clearly illustrated in studies of germ-free (GF) animals [1]. Lathrop et al recently demonstrated that the peripheral T cell population, besides the thymic self/nonself discrimination instructions, further is educated by the colonic microbiota [6]. The microbiota has been shown to influence immune responses to infections as well as the development of noninfectious conditions. The response towards respiratory tract influenza is altered in antibiotic treated animals suggesting the importance of the microbiota in directing the immune responses at other sites than the gut [7]. The microbiota seems to influence development of autoimmune disease [8] and inflammatory bowel disease (IBD) [9] in mice
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