PMID- 29345635
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230813
IS  - 2155-384X (Print)
IS  - 2155-384X (Electronic)
IS  - 2155-384X (Linking)
VI  - 9
IP  - 1
DP  - 2018 Jan 18
TI  - Genetic risk, dysbiosis, and treatment stratification using host genome and gut 
      microbiome in inflammatory bowel disease.
PG  - e132
LID - 10.1038/ctg.2017.58 [doi]
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD) 
      and ulcerative colitis (UC), are characterized by a complex pathophysiology that 
      is thought to result from an aberrant immune response to a dysbiotic luminal 
      microbiota in genetically susceptible individuals. New technologies support the 
      joint assessment of host-microbiome interaction. METHODS: Using whole genome 
      sequencing and shotgun metagenomics, we studied the clinical features, host 
      genome, and stool microbial metagenome of 85 IBD patients, and compared the 
      results to 146 control individuals. Genetic risk scores, computed on 159 single 
      nucleotide variants, and human leukocyte antigen (HLA) types differentiated IBD 
      patients from healthy controls. RESULTS: Genetic risk was associated with the 
      need for use of biologics in IBD and, modestly, with the composition of the gut 
      microbiome. As compared with healthy controls, IBD patients had hallmarks of 
      stool microbiome dysbiosis, with loss of a diversified core microbiome, 
      enrichment and depletion of specific bacteria, and enrichment of bacterial 
      virulence factors. CONCLUSIONS: We show that genetic risk may have a role in 
      early risk stratification in the care of IBD patients and propose that expression 
      of virulence factors in a dysbiotic microbiome may contribute to pathogenesis in 
      IBD.
FAU - Moustafa, Ahmed
AU  - Moustafa A
AD  - Human Longevity Inc., San Diego, CA, USA.
FAU - Li, Weizhong
AU  - Li W
AD  - Human Longevity Inc., San Diego, CA, USA.
AD  - J. Craig Venter Institute, La Jolla, CA, USA.
FAU - Anderson, Ericka L
AU  - Anderson EL
AD  - Human Longevity Inc., San Diego, CA, USA.
FAU - Wong, Emily H M
AU  - Wong EHM
AD  - Human Longevity Inc., San Diego, CA, USA.
FAU - Dulai, Parambir S
AU  - Dulai PS
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
AD  - Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, 
      CA, USA.
FAU - Sandborn, William J
AU  - Sandborn WJ
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
AD  - Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, 
      CA, USA.
FAU - Biggs, William
AU  - Biggs W
AD  - Human Longevity Inc., San Diego, CA, USA.
FAU - Yooseph, Shibu
AU  - Yooseph S
AD  - Human Longevity Inc., San Diego, CA, USA.
FAU - Jones, Marcus B
AU  - Jones MB
AD  - Human Longevity Inc., San Diego, CA, USA.
FAU - Venter, J Craig
AU  - Venter JC
AD  - Human Longevity Inc., San Diego, CA, USA.
AD  - J. Craig Venter Institute, La Jolla, CA, USA.
FAU - Nelson, Karen E
AU  - Nelson KE
AD  - J. Craig Venter Institute, La Jolla, CA, USA.
FAU - Chang, John T
AU  - Chang JT
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
AD  - Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, 
      CA, USA.
FAU - Telenti, Amalio
AU  - Telenti A
AD  - J. Craig Venter Institute, La Jolla, CA, USA.
FAU - Boland, Brigid S
AU  - Boland BS
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
AD  - Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, 
      CA, USA.
LA  - eng
GR  - KL2 TR001444/TR/NCATS NIH HHS/United States
GR  - T32 DK007202/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20180118
PL  - United States
TA  - Clin Transl Gastroenterol
JT  - Clinical and translational gastroenterology
JID - 101532142
PMC - PMC5795019
COIS- Guarantors of the article: Brigid S. Boland and Amalio Telenti. Specific author 
      contributions: Planning the study: KEN, WJS, JTC, AT, BSB. Collecting data: BSB. 
      Generation and analysis of microbiome and genomic data: AM, WL, ELA, EHMW. 
      Sequencing: WB. Interpreting data: AM, WL, AT, JTC, BSB. Drafting manuscript: AM, 
      JTC, AT, BSB. Approval of final draft: AM, WL, ELA, EHMW, PSD, WJS, WB, SY, MBJ, 
      JCV, KEN, JTC, AT, BSB. Financial Support: P.S.D. was supported by US National 
      Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007202). J.T.C was 
      supported by the US National Institutes of Health (DK0935007). B.S.B was 
      supported by the Crohn's and Colitis Foundation and UCSD KL2 (1KL2TR001444). 
      Potential competing interests: WL, ELA, WB, JCV, KEN are employees and stock 
      holders of Human Longevity Inc. There is no intellectual property associated with 
      this work. There are no other competing interests. Data access: The metagenomic 
      data were deposited at NCBI under Bioproject PRJNA423297, available from 
      https://www.ncbi.nlm.nih.gov/bioproject/423297.
EDAT- 2018/01/19 06:00
MHDA- 2018/01/19 06:01
PMCR- 2018/01/01
CRDT- 2018/01/19 06:00
PHST- 2017/07/31 00:00 [received]
PHST- 2017/12/15 00:00 [accepted]
PHST- 2018/01/19 06:00 [entrez]
PHST- 2018/01/19 06:00 [pubmed]
PHST- 2018/01/19 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - ctg201758 [pii]
AID - 10.1038/ctg.2017.58 [doi]
PST - epublish
SO  - Clin Transl Gastroenterol. 2018 Jan 18;9(1):e132. doi: 10.1038/ctg.2017.58.