Compositional maturation of the microbiome and adaptive immunity in the postnatal period.

Introduction: Recent research has highlighted the role of the gut microbiome in shaping the development and function of the mammalian immune system. Interactions between these complex networks of microbes and host cells serve not only to train major aspects of adaptive and innate immunity but also to establish commensal host-microbe relationships and symbiosis throughout the lifespan. T-cells are a critical aspect of this paradigm, acting as intermediates between the microbiome and many aspects of host health and disease. Despite a large body of literature examining these interactions, we have yet to completely understand how the ontogeny of these systems co-evolves across the lifespan and how the emergence of specific T-cell-microbe signals relates to key developmental milestones. Methods: To answer this question, this work conducted a compositional integrative analysis on deep immune and microbiome profiling of wild-type C57Bl/6 mice across the first two weeks of life, post-weaning, and young adulthood. Results: The results show that T-cell ontogeny follows different developmental trends in mucosal and peripheral immune compartments and that temporal trends in microbial community abundance creates a modular network of associations between specific taxa and functional T-cell subsets. Discussion: These results provide insight into the longitudinal development of microbiota-immune system interactions throughout the lifespan, as well as the mechanistic relevance of microbiota-derived signals at key developmental milestones.