Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease

Ahmed Moustafa; Weizhong Li; Ericka L. Anderson; Emily H.M. Wong; Parambir S. Dulai; William J. Sandborn; William Biggs; Shibu Yooseph; Marcus B. Jones; J. Craig Venter; Karen E. Nelson; John T. Chang; Amalio Telenti; Brigid S. Boland

doi:10.1038/ctg.2017.58

Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease

Ahmed Moustafa, Weizhong Li, Ericka L. Anderson, Emily H.M. Wong, Parambir S. Dulai, William J. Sandborn, William Biggs, Shibu Yooseph, Marcus B. Jones, J. Craig Venter^*, Karen E. Nelson, John T. Chang, Amalio Telenti, Brigid S. Boland

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e132
Journal	Clinical and translational gastroenterology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/ctg.2017.58
State	Published - Jan 18 2018

Funding

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.

ASJC Scopus subject areas

Gastroenterology

Access to Document

10.1038/ctg.2017.58

Cite this

Moustafa, A., Li, W., Anderson, E. L., Wong, E. H. M., Dulai, P. S., Sandborn, W. J., Biggs, W., Yooseph, S., Jones, M. B., Venter, J. C., Nelson, K. E., Chang, J. T., Telenti, A., & Boland, B. S. (2018). Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease. Clinical and translational gastroenterology, 9(1), Article e132. https://doi.org/10.1038/ctg.2017.58

@article{8f1850bb3b2e4b20be8190fc72335d7d,

title = "Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease",

abstract = "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.",

author = "Ahmed Moustafa and Weizhong Li and Anderson, {Ericka L.} and Wong, {Emily H.M.} and Dulai, {Parambir S.} and Sandborn, {William J.} and William Biggs and Shibu Yooseph and Jones, {Marcus B.} and Venter, {J. Craig} and Nelson, {Karen E.} and Chang, {John T.} and Amalio Telenti and Boland, {Brigid S.}",

note = "Funding Information: 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{\textquoteright}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. Publisher Copyright: {\textcopyright} The Author(s) 2018.",

year = "2018",

month = jan,

day = "18",

doi = "10.1038/ctg.2017.58",

language = "English (US)",

volume = "9",

journal = "Clinical and translational gastroenterology",

issn = "2155-384X",

publisher = "Nature Publishing Group",

number = "1",

}

Moustafa, A, Li, W, Anderson, EL, Wong, EHM, Dulai, PS, Sandborn, WJ, Biggs, W, Yooseph, S, Jones, MB, Venter, JC, Nelson, KE, Chang, JT, Telenti, A & Boland, BS 2018, 'Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease', Clinical and translational gastroenterology, vol. 9, no. 1, e132. https://doi.org/10.1038/ctg.2017.58

TY - JOUR

T1 - Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease

AU - Moustafa, Ahmed

AU - Li, Weizhong

AU - Anderson, Ericka L.

AU - Wong, Emily H.M.

AU - Dulai, Parambir S.

AU - Sandborn, William J.

AU - Biggs, William

AU - Yooseph, Shibu

AU - Jones, Marcus B.

AU - Venter, J. Craig

AU - Nelson, Karen E.

AU - Chang, John T.

AU - Telenti, Amalio

AU - Boland, Brigid S.

N1 - Funding Information: 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. Publisher Copyright: © The Author(s) 2018.

PY - 2018/1/18

Y1 - 2018/1/18

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85040827564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040827564&partnerID=8YFLogxK

U2 - 10.1038/ctg.2017.58

DO - 10.1038/ctg.2017.58

M3 - Article

C2 - 29345635

AN - SCOPUS:85040827564

SN - 2155-384X

VL - 9

JO - Clinical and translational gastroenterology

JF - Clinical and translational gastroenterology

IS - 1

M1 - e132

ER -

Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this