ena-STUDY-The Edison Family Center of Genome Sciences and Systems Biology-01-05-2018-20:52:54:803-6
Identifying determinants of bacterial fitness in a model of human gut microbial succession
Human gut microbiota development has been associated with healthy growth but understanding the determinants of community assembly and composition is a formidable challenge. We cultured bacteria from serially-collected fecal samples from a healthy infant; 34 sequenced strains containing 103,102 genes were divided into two consortia representing earlier and later stages in community assembly during the first 6 postnatal months. The two consortia were introduced alone (singly), or sequentially in different order, or simultaneously into young germ-free mice fed human infant formula. The pattern of fitness of bacterial strains observed across the different colonization conditions indicated that later phase strains substantially out-compete earlier phase strains, although four early phase members persist. Persistence was not determined by order of introduction, suggesting that priority effects are not prominent in this model. To characterize succession in the context of the metabolic potential of consortium members, we performed in silico reconstructions of metabolic pathways involved in utilization of mono-, di- and oligosaccharides, and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially-collected fecal samples, their transcriptional responses to different histories of colonization. Applying feature-reduction methods disclosed a set of metabolic pathways whose presence and/or expression correlates with strain fitness and that enable early stage colonizers to survive during introduction of later colonizers. In principle, the approach described can be used to study various ecological processes that govern gut community assembly and to facilitate development of microbiota-directed therapeutics.
Human gut microbiota development has been associated with healthy growth but understanding the determinants of community assembly and composition is a formidable challenge. We cultured bacteria from serially-collected fecal samples from a healthy infant; 34 sequenced strains containing 103,102 genes were divided into two consortia representing earlier and later stages in community assembly during the first 6 postnatal months. The two consortia were introduced alone (singly), or sequentially in different order, or simultaneously into young germ-free mice fed human infant formula. The pattern of fitness of bacterial strains observed across the different colonization conditions indicated that later phase strains substantially out-compete earlier phase strains, although four early phase members persist. Persistence was not determined by order of introduction, suggesting that priority effects are not prominent in this model. To characterize succession in the context of the metabolic potential of consortium members, we performed in silico reconstructions of metabolic pathways involved in utilization of mono-, di- and oligosaccharides, and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially-collected fecal samples, their transcriptional responses to different histories of colonization. Applying feature-reduction methods disclosed a set of metabolic pathways whose presence and/or expression correlates with strain fitness and that enable early stage colonizers to survive during introduction of later colonizers. In principle, the approach described can be used to study various ecological processes that govern gut community assembly and to facilitate development of microbiota-directed therapeutics.