Nutrient resource prioritization in the human gut microbiota. Inducible CRISPR-targeted ‘knockdown’ of human gut Bacteroides in gnotobiotic mice discloses glycan utilization strategies

Learning how human gut bacteria compete and cooperate to metabolize nutrients is an important step towards developing more nutritious foods and promoting healthier gut microbial communities. Human gut Bacteroidaceae are primary consumers of complex dietary polysaccharides. Here we describe a genetic system for deliberately inducing a decrease in the abundance of a target organism in a gut community. Gnotobiotic mice were fed a human diet and colonized with a defined community of cultured, genome-sequenced, human gut bacteria, including multiple Bacteroidaceae species. ‘Knockdowns’ of different Bacteroides within the established community resulted in specific increases in the abundances of other organisms and revealed how they dynamically changed their priorities for utilizing available polysaccharides while preserving the community’s overall capacity to metabolize carbohydrates.