Understanding the interplay of intestinal microbiota, IgA response and human disease

This thesis aimed to increase the understanding of mucosal immune responses in health and disease, with a special focus on IgA antibody responses and how intestinal bacteria affect adaptive immune responses.
Healthy adults (Chapter 2) and children (Chapter 3) were each classified into three groups (enterotypes) on the basis of distinct intestinal microbiota compositions. In adults, several types of blood immune cells, especially helper T cells differed between enterotypes. Detailed evaluation of the intestinal microbiota and the B- and T-cell compartments in a large cohort (n= 344) of 10-year-old children of the Generation R cohort enabled us to take confounders as BMI, ethnicity, diet, child´s sex and household income into account. Children with the Blautia enterotype showed alterations in various T-cell subsets and memory B cells.
In children with atopic disease, we found increased helper T-cells and IgA+ memory B cells, whereas IgE+ memory B cells were normal (Chapter 4). In food allergies, specifically T-cell dependent derived IgA+ memory B cells were increased. These results indicate that IgA plays also a role in atopic diseases.
In contrast, in patients with selective IgA deficiency decreased IgA+ memory B cells were found (Chapter 5). Increased helper T cells and cytokine concentrations in blood with normal B-cell activation are suggestive of a B-cell extrinsic defect, and a disturbance in the regulation of the IgA response.
Overall, we provided valuable insights about the immune response in healthy individuals in light of distinct intestinal bacteria and in disease.