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Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2622-2633. doi: 10.1073/pnas.1918951117. Epub 2020 Jan 22.

Identifying determinants of bacterial fitness in a model of human gut microbial succession.

Author information

1
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110.
2
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110.
3
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110; jgordon@wustl.edu.
4
A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, 127994 Moscow, Russia.
5
Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037.

Abstract

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 six 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 outcompete 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 carbohydrate utilization and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially collected fecal samples and 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. The approach described can be used to test the magnitude of the contribution of identified metabolic pathways to fitness in different community contexts, study various ecological processes thought to govern community assembly, and facilitate development of microbiota-directed therapeutics.

KEYWORDS:

feature-reduction algorithms; gut microbiome; metabolic pathways; microbial community assembly/succession

Conflict of interest statement

Competing interest statement: J.I.G. is a cofounder of Matatu, Inc., a company characterizing the role of diet-by-microbiota interactions in animal health.

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