title: Effects of diet on resource utilization by a model human gut microbiota containing Bacteroides cellulosilyticus WH2, a symbiont with an extensive glycobiome.
abstract: The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism's 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight into how gut microbes adapt to dietary perturbations at both a community level and from the perspective of a well-adapted symbiont with exceptional saccharolytic capabilities, and illustrate the value of artificial communities.
authors: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: Nathan P
authors: NP
authors: McNulty
authors: Meng
authors: M
authors: Wu
authors: Alison R
authors: AR
authors: Erickson
authors: Chongle
authors: C
authors: Pan
authors: Brian K
authors: BK
authors: Erickson
authors: Eric C
authors: EC
authors: Martens
authors: Nicholas A
authors: NA
authors: Pudlo
authors: Brian D
authors: BD
authors: Muegge
authors: Bernard
authors: B
authors: Henrissat
authors: Robert L
authors: RL
authors: Hettich
authors: Jeffrey I
authors: JI
authors: Gordon
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000235:genetics* / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D064307:Microbiota / Q000235:genetics / Q000502:physiology*; D013559:Symbiosis
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