ABSTRACT
Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex but not both, limiting their utility. In accompanying work, we constructed a complex synthetic community (104 strains, hCom1) containing the most common taxa in the human gut microbiome. Here, we used an iterative experimental process to improve hCom1 by filling open metabolic and/or anatomical niches. When we colonized germ-free mice with hCom1 and then challenged it with a human fecal sample, the consortium exhibited surprising stability; 89% of the cells and 58% of the taxa derive from the original community, and the pre- and post-challenge communities share a similar overall structure. We used these data to construct a second version of the community, adding 22 strains that engrafted following fecal challenge and omitting 7 that dropped out (119 strains, hCom2). In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by hCom2 versus human feces are similar in terms of microbiota-derived metabolites, immune cell profile, and bacterial density in the gut, suggesting that this consortium is a prototype of a model system for the human gut microbiome.
Competing Interest Statement
Stanford University and the Chan Zuckerberg Biohub have patents pending for microbiome technologies on which the authors are co-inventors. M.A.F. is a co-founder and director of Federation Bio and Viralogic, a co-founder of Revolution Medicines, and a member of the scientific advisory boards of NGM Bio and Zymergen. A.G.C. and K.N. have been paid consultants to Federation Bio. A.R.B. is an employee of Federation Bio. All of the other authors have no competing interests.
Footnotes
Lead author: Michael Fischbach (fischbach{at}fischbachgroup.org)