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Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice

Joseph D. Planer,Yangqing Peng,Andrew L. Kau,Laura V. Blanton,I. Ndao,Phillip I. Tarr,Barbara B. Warner,J. I. Gordon

Published 2016 in Nature

ABSTRACT

The relationship between assembly of the gut community and gut mucosal immunoglobulin A responses during the first 24–36 months of postnatal life in a cohort of 40 twin pairs is defined and modelled in gnotobiotic mice. Mucosal immunoglobulin A (IgA) is the major antibody class produced in the gut, but it is not clear how IgA responses co-develop with assembly of the microbiota post-natally. Jeffrey Gordon and colleagues define the relationship between assembly of the gut community and gut mucosal IgA responses during the first 24 to 36 months of postnatal life in a cohort of 40 twin pairs. They identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly. The pattern of maturation of gut mucosal IgA responses to the microbiota is highly distinct for different twin pairs during the first several postnatal months, but generalizes across pairs in the second year of life. Age-associated differences in these IgA responses were recapitulated in mice colonized with faecal microbiota from the infants and fed human diets that simulate the transition from milk feeding to complementary foods. These data suggest that co-development is largely independent of diet and that 'intrinsic' properties of the microbiota have a dominant role in dictating IgA responses. Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function1,2,3. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways4,5, plus glycans present on the antibody’s secretory component6. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice7,8. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA9,10,11. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that ‘intrinsic’ properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity.

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