Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease
Background: Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently d...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/72428 https://orcid.org/0000-0001-8294-9364 https://orcid.org/0000-0002-8202-5222 |
| _version_ | 1811068629995749376 |
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| author | Papa, Eli Docktor, Michael Smillie, Christopher Weber, Sarah Preheim, Sarah Pacocha Gevers, Dirk Giannoukos, Georgia Ciulla, Dawn Tabbaa, Diana Ingram, Jay Schauer, David B. Ward, Doyle V. Korzenik, Joshua R. Xavier, Ramnik J. Bousvaros, Athos Alm, Eric J. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Papa, Eli Docktor, Michael Smillie, Christopher Weber, Sarah Preheim, Sarah Pacocha Gevers, Dirk Giannoukos, Georgia Ciulla, Dawn Tabbaa, Diana Ingram, Jay Schauer, David B. Ward, Doyle V. Korzenik, Joshua R. Xavier, Ramnik J. Bousvaros, Athos Alm, Eric J. |
| author_sort | Papa, Eli |
| collection | MIT |
| description | Background:
Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders.
Methodology/Principal Findings:
We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children’s Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn’s disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity).
Conclusions/Significance:
Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients. |
| first_indexed | 2024-09-23T07:58:48Z |
| format | Article |
| id | mit-1721.1/72428 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T07:58:48Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/724282022-09-30T01:27:11Z Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease Papa, Eli Docktor, Michael Smillie, Christopher Weber, Sarah Preheim, Sarah Pacocha Gevers, Dirk Giannoukos, Georgia Ciulla, Dawn Tabbaa, Diana Ingram, Jay Schauer, David B. Ward, Doyle V. Korzenik, Joshua R. Xavier, Ramnik J. Bousvaros, Athos Alm, Eric J. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Alm, Eric J. Papa, Eli Smillie, Christopher Weber, Sarah Preheim, Sarah Pacocha Schauer, David B. Alm, Eric J. Background: Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders. Methodology/Principal Findings: We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children’s Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn’s disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity). Conclusions/Significance: Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients. Natural Sciences and Engineering Research Council of Canada (Award NSERC PGS D) National Institutes of Health (U.S.) (1-R21-A1084032-01A1) 2012-08-29T18:04:42Z 2012-08-29T18:04:42Z 2012-06 2012-03 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/72428 Papa, Eliseo et al. “Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease.” Ed. Jacques Ravel. PLoS ONE 7.6 (2012): e39242. https://orcid.org/0000-0001-8294-9364 https://orcid.org/0000-0002-8202-5222 en_US http://dx.doi.org/10.1371/journal.pone.0039242 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Papa, Eli Docktor, Michael Smillie, Christopher Weber, Sarah Preheim, Sarah Pacocha Gevers, Dirk Giannoukos, Georgia Ciulla, Dawn Tabbaa, Diana Ingram, Jay Schauer, David B. Ward, Doyle V. Korzenik, Joshua R. Xavier, Ramnik J. Bousvaros, Athos Alm, Eric J. Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease |
| title | Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease |
| title_full | Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease |
| title_fullStr | Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease |
| title_full_unstemmed | Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease |
| title_short | Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease |
| title_sort | non invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease |
| url | http://hdl.handle.net/1721.1/72428 https://orcid.org/0000-0001-8294-9364 https://orcid.org/0000-0002-8202-5222 |
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