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Genome Med. 2017 Nov 28;9(1):103. doi: 10.1186/s13073-017-0490-5.

A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients.

Author information

1
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
2
Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
3
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
4
Current address: Vatche and Tamar Manoukian Division of Digestive Disease, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
5
Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
6
MIT Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
7
Emory University School of Medicine, Emory University, Atlanta, GA, 30322, USA.
8
Current address: Janssen Human Microbiome Institute, Janssen Research & Development, Cambridge, MA, 02142, USA.
9
MIT Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
10
Department of Systems Biology, Harvard Medical School, Boston, MA, 02114, USA.
11
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. xavier@molbio.mgh.harvard.edu.
12
Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. xavier@molbio.mgh.harvard.edu.
13
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. xavier@molbio.mgh.harvard.edu.
14
Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. xavier@molbio.mgh.harvard.edu.
15
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. chuttenh@hsph.harvard.edu.
16
Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA. chuttenh@hsph.harvard.edu.

Abstract

BACKGROUND:

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes.

METHODS:

We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn.

RESULTS:

We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut.

CONCLUSIONS:

This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.

PMID:
29183332
PMCID:
PMC5704459
DOI:
10.1186/s13073-017-0490-5
[Indexed for MEDLINE]
Free PMC Article

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