Journal Article

Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides

Griffin, Nicholas W., Kerstetter, Randall A., Henrissat, Bernard, Osterman, Andrei L., Cheng, Jiye, Rodionov, Dmitry A., McNulty, Nathan P., Gordon, Jeffrey I., Khoroshkin, Matvei S., Wu, Meng, Latreille, Phil, Terrapon, Nicolas

2015

Overview

The human gut microbiota is hugely diverse, with many strain variants having a multiplicity of effects on host metabolism and immunity. To define some of these functions, Wu et al. made libraries of mutants of Bacteroides species known for their capacity to process otherwise intractable dietary fiber. Germ-free mice colonized with defined gut microbiota communities containing the mutants were fed specific diets containing different ratios of fat and fiber. Genes, strains, and species were identified that were associated with specific metabolic pathways. The community responses to dietary shifts were manipulated in an attempt to characterize species for their probiotic or therapeutic potential. Science , this issue 10.1126/science.aac5992 > To design probiotics, gut microbe fitness determinants and niches were characterized and responses to dietary changes monitored. Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)
• Subject: Amino acids / Animals / Bacteroides / Bacteroides - genetics / Bacteroides - metabolism / Biochemistry, Molecular Biology / Carbohydrates / Communities / Community Relations / Community structure / Determinants / Diet / Dietary fiber / Diets / DNA Transposable Elements - genetics / Drinking water / Fibers / Fitness / Gastrointestinal Tract - microbiology / Gene Library / Genetic factors / Genetic Fitness - genetics / Genetic Loci / Genetic Markers / Genetics / Germ-Free Life / Human behavior / Humans / Introduced species / Libraries / Life Sciences / Literary Devices / Mice / Mutagenesis, Insertional - methods / Mutants / Niches / Prebiotics / Quantitative Methods / Relative abundance / RESEARCH ARTICLE SUMMARY / Saccharides / Sequence Analysis, DNA - methods / Structural Biology / Sugar / Taxa / Vitamins / Xylans - metabolism