Format

Send to

Choose Destination
Sci Transl Med. 2009 Nov 11;1(6):6ra14. doi: 10.1126/scitranslmed.3000322.

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

Author information

1
Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108, USA.

Abstract

Diet and nutritional status are among the most important modifiable 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's microbiota. 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 the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will 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. Nearly full-length 16S rRNA gene sequences are deposited in GenBank under the accession numbers GQ491120 to GQ493997.

PMID:
20368178
PMCID:
PMC2894525
DOI:
10.1126/scitranslmed.3000322
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substance, Secondary source ID, Grant support

Publication types

MeSH terms

Substance

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center