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| Status |
Public on Aug 20, 2013 |
| Title |
Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome (GeneChip) |
| Platform organisms |
Bacteroides thetaiotaomicron VPI-5482; Bacteroides sp. WH2; Blautia obeum ATCC 29174; [Ruminococcus] torques ATCC 27756; Dorea longicatena DSM 13814; [Clostridium] scindens ATCC 35704; Bacteroides ovatus ATCC 8483; Bacteroides uniformis ATCC 8492; Faecalibacterium prausnitzii M21/2; Bacteroides caccae ATCC 43185; Collinsella aerofaciens ATCC 25986; Thomasclavelia spiroformis DSM 1552; Phocaeicola vulgatus ATCC 8482; Parabacteroides distasonis ATCC 8503; Agathobacter rectalis ATCC 33656 |
| Sample organisms |
Bacteroides thetaiotaomicron VPI-5482; Bacteroides sp. WH2; Blautia obeum ATCC 29174; Dorea longicatena DSM 13814; [Clostridium] scindens ATCC 35704; Bacteroides ovatus ATCC 8483; Bacteroides uniformis ATCC 8492; Bacteroides caccae ATCC 43185; Collinsella aerofaciens ATCC 25986; Thomasclavelia spiroformis DSM 1552; Phocaeicola vulgatus ATCC 8482; Parabacteroides distasonis ATCC 8503 |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
An artificial community of 12 human gut bacterial species was introduced into germ-free male C57BL/6J mice at 10-12 weeks of age. Mice were split into two treatment groups, with each treatment group receiving an oscillating diet regimen in which animals were switched between a low fat, high plant polysaccharide (LF/HPP) diet and a high fat, high sugar (HF/HS) diet at two week intervals. One group was started on the LF/HPP diet, was switched to the HF/HS diet, and was then switched back to the LF/HPP diet. The other group was started on the HF/HS diet, was switched to the LF/HPP diet, and was then switched back to the HF/HS diet. Cecal contents were collected from each animal at the time of sacrifice which corresponded to the end of each treatment group's third diet phase. Separate gene expression profiles for each of the 12 species in the artificial community were generated for each sample using a series of custom mask files. 14 total samples (7 from animals consuming the LF/HPP diet at the time of sacrifice, 7 from animals consuming the HF/HS diet at the time of sacrifice). 12 gene expression profiles per sample (1/species).
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| Contributor(s) |
McNulty NP |
| Citation(s) |
23976882 |
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| Submission date |
Jul 03, 2013 |
| Last update date |
Nov 19, 2013 |
| Contact name |
Nathan P McNulty |
| E-mail(s) |
nathan.p.mcnulty@gmail.com
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| Phone |
314-362-3963
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| Organization name |
Washington University School of Medicine
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| Department |
Center for Genome Sciences and Systems Biology
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| Lab |
Gordon
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| Street address |
4444 Forest Park Ave. (5th Floor)
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| City |
Saint Louis |
| State/province |
MO |
| ZIP/Postal code |
63108 |
| Country |
USA |
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| Platforms (1) |
| GPL9803 |
[SynComm1a520717] SynComm1: Synthetic Human Gut Community GeneChip, v1.0 |
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| Samples (168)
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| This SubSeries is part of SuperSeries: |
| GSE48537 |
Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome |
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| Relations |
| BioProject |
PRJNA210444 |
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