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

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 techno...

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Autores principales: Moustafa, Ahmed, Li, Weizhong, Anderson, Ericka L, Wong, Emily H M, Dulai, Parambir S, Sandborn, William J, Biggs, William, Yooseph, Shibu, Jones, Marcus B, Venter, J Craig, Nelson, Karen E, Chang, John T, Telenti, Amalio, Boland, Brigid S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795019/
https://www.ncbi.nlm.nih.gov/pubmed/29345635
http://dx.doi.org/10.1038/ctg.2017.58
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author Moustafa, Ahmed
Li, Weizhong
Anderson, Ericka L
Wong, Emily H M
Dulai, Parambir S
Sandborn, William J
Biggs, William
Yooseph, Shibu
Jones, Marcus B
Venter, J Craig
Nelson, Karen E
Chang, John T
Telenti, Amalio
Boland, Brigid S
author_facet Moustafa, Ahmed
Li, Weizhong
Anderson, Ericka L
Wong, Emily H M
Dulai, Parambir S
Sandborn, William J
Biggs, William
Yooseph, Shibu
Jones, Marcus B
Venter, J Craig
Nelson, Karen E
Chang, John T
Telenti, Amalio
Boland, Brigid S
author_sort Moustafa, Ahmed
collection PubMed
description 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.
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spelling pubmed-57950192018-02-15 Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease Moustafa, Ahmed Li, Weizhong Anderson, Ericka L Wong, Emily H M Dulai, Parambir S Sandborn, William J Biggs, William Yooseph, Shibu Jones, Marcus B Venter, J Craig Nelson, Karen E Chang, John T Telenti, Amalio Boland, Brigid S Clin Transl Gastroenterol Original Contributions 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. Nature Publishing Group 2018-01 2018-01-18 /pmc/articles/PMC5795019/ /pubmed/29345635 http://dx.doi.org/10.1038/ctg.2017.58 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Contributions
Moustafa, Ahmed
Li, Weizhong
Anderson, Ericka L
Wong, Emily H M
Dulai, Parambir S
Sandborn, William J
Biggs, William
Yooseph, Shibu
Jones, Marcus B
Venter, J Craig
Nelson, Karen E
Chang, John T
Telenti, Amalio
Boland, Brigid S
Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
title Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
title_full Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
title_fullStr Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
title_full_unstemmed Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
title_short Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
title_sort genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease
topic Original Contributions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795019/
https://www.ncbi.nlm.nih.gov/pubmed/29345635
http://dx.doi.org/10.1038/ctg.2017.58
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