Abstract

Dynamics of metatranscription in the inflammatory bowel disease gut microbiome

Schirmer M1,2, Franzosa EA1,2, Lloyd-Price J1,2, McIver LJ1,2, Schwager R2, Poon TW1, Ananthakrishnan AN3, Andrews E3, Barron G4, Lake K5, Prasad M6, Sauk J3,7, Stevens B3, Wilson RG3, Braun J8, Denson LA5, Kugathasan S6,9, McGovern DPB4, Vlamakis H1, Xavier RJ10,11,12,13, Huttenhower C14,15. Nat Microbiol. 2018 Jan 8. doi: 10.1038/s41564-017-0089-z. [Epub ahead of print]
 
     

Author information

1 The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

2 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

3 Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA.

4 The F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

5 Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

6 Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, GA, USA.

7 Vatche and Tamar Manoukian Division of Digestive Disease, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

8 Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

9 Children's Healthcare of Atlanta, Atlanta, GA, USA.

10 The Broad Institute of MIT and Harvard, Cambridge, MA, USA. rxavier@broadinstitute.org.

11 Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA. rxavier@broadinstitute.org.

12 Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA. rxavier@broadinstitute.org.

13 Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA. rxavier@broadinstitute.org.

14 The Broad Institute of MIT and Harvard, Cambridge, MA, USA. chuttenh@hsph.harvard.edu.

15 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. chuttenh@hsph.harvard.edu.

Abstract

Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.

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