The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice

Peter J. Turnbaugh, Vanessa K. Ridaura, Jeremiah J. Faith, Federico E. Rey, Rob Knight, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

1933 Scopus citations

Abstract

Diet and nutritional status are among themost importantmodifiable determinants of human health. The nutritional value of food is influenced in part by a person's gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor'smicrobiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat, high-sugar "Western" diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of themicrobial community but that these effects can be rapidly altered by diet. Humanizedmice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobioticmicewill be useful for conducting proof-of-principle "clinical trials" that test the effects of environmental and genetic factors on the gut microbiota and host physiology.

Original languageEnglish
Article number6ra14
JournalScience translational medicine
Volume1
Issue number6
DOIs
StatePublished - Nov 11 2009

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