Infant gut microbiota, immune responses and allergic disease during childhood

Abstract: The early-life microbiota is important for postnatal immune maturation and implied in immune mediated diseases. The aim of this work was to study specific species of bacteria in the gut microbiota and relate them to immune function and allergic disease during childhood.In paper I we investigated gut bacteria in feces from infants included in a prospective allergy cohort. We found that children with non-allergic parents were more likely to be colonized with a group of lactobacilli. Further, lactobacilli colonization was more prevalent in children remaining non-allergic, regardless of allergic heredity. In paper II we related the infant gut bacteria to immune function at two years of age. Infant Staphylococcus (S.) aureus colonization associated with increased immune responsiveness, whereas co-colonization with S. aureus and lactobacilli associated with reduced responses. In paper III we investigated T regulatory (Treg) cell phenotype and cytokine production during childhood, and related S. aureus and lactobacilli colonization to Treg phenotype at the age of two. The Treg population matured with age, regarding phenotype and cytokine production. Furthermore, infant S. aureus colonization associated with Treg phenotype at the age of two. In paper IV we investigated the in vitro peripheral blood mononuclear cells responses to soluble factors produced by lactobacilli and S. aureus. Both T- and natural killer cells responded with cytokine production, degranulation and proliferation after S. aureus and simultaneous culture with lactobacilli could dampen the S. aureus-induced responses.Taken together this thesis shows that the gut microbiota is altered in children who develop allergies, and that early life bacteria associate with immune function. Our in vitro findings support that lactobacilli modulate immune maturation and responses, and that early lactobacilli-colonization may be important for a properly regulated maturation of the immune system.