Longitudinal gut microbial trajectories show differences in early life LPS exposure and IFNγ responses 4153

Abstract Description Substantial evidence suggests a central role for the gut microbiome as an important regulator of early life immune development. Because microbial abundances constantly change with time as a result of extrinsic and intrinsic factors, it is hard to account for their temporal dynamics. To address this, we applied an unsupervised method to cluster infants according to their longitudinal microbial colonization trajectories in a unique analysis. Our cohort consists of longitudinal gut metagenomes (n = 966) during the first year of life from 278 infants. 156 infants are additionally paired with longitudinal Olink and CyTOF data from blood. We demonstrate how colonization trajectories for the major classes of gut bacteria behave, and how infants fall along different paths. Bacteroidia trajectory affiliation explained most of the compositional variation in the entire microbiome, and these trajectories converged with age. We have previously demonstrated that infants have an IFNγ spike during the first week of life (Henrick et al., Cell, 2021). Here we show that Bacteroidia trajectories separate infants with high and low IFNγ responses. This indicates that the IFNγ spike is influenced by microbial colonization. We continue to show that infants across Bacteroidia trajectories have vastly different loads of gram- and gram+ gut bacteria during this window. Suggesting large differences in early life exposure to endotoxin and other microbial components. Topic Categories Mucosal and Regional Immunology (MUC)