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A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?

BACKGROUND: Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable...

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Autores principales: Forbes, Jessica D., Chen, Chih-yu, Knox, Natalie C., Marrie, Ruth-Ann, El-Gabalawy, Hani, de Kievit, Teresa, Alfa, Michelle, Bernstein, Charles N., Van Domselaar, Gary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292067/
https://www.ncbi.nlm.nih.gov/pubmed/30545401
http://dx.doi.org/10.1186/s40168-018-0603-4
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author Forbes, Jessica D.
Chen, Chih-yu
Knox, Natalie C.
Marrie, Ruth-Ann
El-Gabalawy, Hani
de Kievit, Teresa
Alfa, Michelle
Bernstein, Charles N.
Van Domselaar, Gary
author_facet Forbes, Jessica D.
Chen, Chih-yu
Knox, Natalie C.
Marrie, Ruth-Ann
El-Gabalawy, Hani
de Kievit, Teresa
Alfa, Michelle
Bernstein, Charles N.
Van Domselaar, Gary
author_sort Forbes, Jessica D.
collection PubMed
description BACKGROUND: Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn’s disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach. RESULTS: Significant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance. CONCLUSIONS: This study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0603-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-62920672018-12-17 A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist? Forbes, Jessica D. Chen, Chih-yu Knox, Natalie C. Marrie, Ruth-Ann El-Gabalawy, Hani de Kievit, Teresa Alfa, Michelle Bernstein, Charles N. Van Domselaar, Gary Microbiome Research BACKGROUND: Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn’s disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach. RESULTS: Significant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance. CONCLUSIONS: This study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0603-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-13 /pmc/articles/PMC6292067/ /pubmed/30545401 http://dx.doi.org/10.1186/s40168-018-0603-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Forbes, Jessica D.
Chen, Chih-yu
Knox, Natalie C.
Marrie, Ruth-Ann
El-Gabalawy, Hani
de Kievit, Teresa
Alfa, Michelle
Bernstein, Charles N.
Van Domselaar, Gary
A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
title A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
title_full A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
title_fullStr A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
title_full_unstemmed A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
title_short A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
title_sort comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292067/
https://www.ncbi.nlm.nih.gov/pubmed/30545401
http://dx.doi.org/10.1186/s40168-018-0603-4
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