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Fujimura, K. E.

Publications and source records attributed to Fujimura, K. E..

2 recordsLinked to original sources

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Analysis of 1,363 deeply sequenced gut microbiome samples from 946 healthy donors of the Milieu Interieur cohort provides new opportunities to discover how the gut microbiome is associated with host factors and lifestyle parameters. Using a genome-based taxonomy to achieve higher resolution analysis, we found an enrichment of Prevotella species in males, and that bacterial profiles are dynamic across five decades of life (20-69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed short-term stability exceeds inter-individual differences; however, the degree of stability was variable between donors and influenced by their baseline community composition. We then integrated the microbiome results with systemic immunophenotypes to show that host/microbe associations discovered in animal models, such as T regulatory cells and short chain fatty acids, could be validated in human data. These results will enable personalized medicine approaches for microbial therapeutics and biomarkers.

microbiology↗

Neonatal gut-microbiome-derived 12,13 DiHOME impedes tolerance and promotes childhood atopy and asthma

Neonates at risk of childhood atopy and asthma are characterized by gut microbiome perturbation and fecal enrichment of 12,13 DiHOME(1); however, the underlying mechanism and source of this metabolite remain poorly understood. Here we show that 12,13 DiHOME treatment of human dendritic cells altered peroxisome proliferator-activated receptor {gamma} regulated gene expression and decreased immune tolerance. In mice, 12,13 DiHOME treatment prior to airway challenge exacerbated pulmonary inflammation and decreased lung regulatory T cells. Neonatal fecal metagenomic sequencing revealed putative bacterial sources of 12,13 DiHOME. In our cohort, three bacterial genes and their product, 12,13 DiHOME, are associated with increased odds of childhood atopy or asthma, suggesting that early-life gut-microbiome risk factors may shape immune tolerance and identify high-risk neonates years in advance of clinical symptoms.\n\nOne Sentence SummaryEarly-life gut-microbiome risk factors may shape immune tolerance and identify neonates at high-risk of disease.

microbiology↗