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16S sequencing and functional analysis of the faecal microbiome during treatment of newly diagnosed paediatric inflammatory bowel disease

16S sequencing and functional analysis of the faecal microbiome during treatment of newly diagnosed paediatric inflammatory bowel disease
16S sequencing and functional analysis of the faecal microbiome during treatment of newly diagnosed paediatric inflammatory bowel disease
The human microbiome is of considerable interest to pediatric inflammatory bowel disease (PIBD) researchers with 1 potential mechanism for disease development being aberrant immune handling of the intestinal bacteria. This study analyses the fecal microbiome through treatment in newly diagnosed PIBD patients and compares to cohabiting siblings where possible. Patients were recruited on clinical suspicion of PIBD before diagnosis. Treatment-naïve fecal samples were collected, with further samples at 2 and 6 weeks into treatment. Samples underwent 16S ribosomal ribonucleic acid (RNA) gene sequencing and short-chain fatty acids (SCFAs) analysis, results were analyzed using quantitative-insights-into-microbial-ecology. Six PIBD patients were included in the cohort: 4 Crohn disease (CD), 1 ulcerative colitis (UC), 1 inflammatory bowel disease (IBD) unclassified, and median age 12.6 (range 10–15.1 years); 3 patients had an unaffected healthy sibling recruited. Microbial diversity (observed species/Chao1/Shannon diversity) was reduced in treatment-naïve patients compared to siblings and patients in remission. Principal coordinate analysis using Bray–Curtis dissimilarity and UniFrac revealed microbial shifts in CD over the treatment course. In treatment-naïve PIBD, there was reduction in functional ability for amino acid metabolism and carbohydrate handling compared to controls (P = .038) and patients in remission (P = .027). Metabolic function returned to normal after remission was achieved. SCFA revealed consistent detection of lactate in treatment-naïve samples. This study adds in-depth 16S rRNA sequencing analysis on a small longitudinal cohort to the literature and includes sibling controls and patients with UC/IBD unclassified. It highlights the initial dysbiosis, reduced diversity, altered functional potential, and subsequent shifts in bacteria from diagnosis over time to remission.
1357-3039
Ashton, James J.
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Colquhoun, Catherine M.
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Cleary, David
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Coelho, Tracy
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Haggarty, Rachel
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Mulder, Imke
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Batra, Akshay
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Afzal, Nadeem
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Beattie, R. Mark
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Scott, Karen P.
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Ennis, Sarah
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Ashton, James J.
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Colquhoun, Catherine M.
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Cleary, David
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Coelho, Tracy
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Haggarty, Rachel
d79fd59d-2cdc-465a-93e4-b0aeb78583c6
Mulder, Imke
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Batra, Akshay
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Afzal, Nadeem
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Beattie, R. Mark
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Scott, Karen P.
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Ennis, Sarah
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Ashton, James J., Colquhoun, Catherine M., Cleary, David, Coelho, Tracy, Haggarty, Rachel, Mulder, Imke, Batra, Akshay, Afzal, Nadeem, Beattie, R. Mark, Scott, Karen P. and Ennis, Sarah (2017) 16S sequencing and functional analysis of the faecal microbiome during treatment of newly diagnosed paediatric inflammatory bowel disease Medicine, 96, (26) (doi:10.1097/MD.0000000000007347).

Record type: Article

Abstract

The human microbiome is of considerable interest to pediatric inflammatory bowel disease (PIBD) researchers with 1 potential mechanism for disease development being aberrant immune handling of the intestinal bacteria. This study analyses the fecal microbiome through treatment in newly diagnosed PIBD patients and compares to cohabiting siblings where possible. Patients were recruited on clinical suspicion of PIBD before diagnosis. Treatment-naïve fecal samples were collected, with further samples at 2 and 6 weeks into treatment. Samples underwent 16S ribosomal ribonucleic acid (RNA) gene sequencing and short-chain fatty acids (SCFAs) analysis, results were analyzed using quantitative-insights-into-microbial-ecology. Six PIBD patients were included in the cohort: 4 Crohn disease (CD), 1 ulcerative colitis (UC), 1 inflammatory bowel disease (IBD) unclassified, and median age 12.6 (range 10–15.1 years); 3 patients had an unaffected healthy sibling recruited. Microbial diversity (observed species/Chao1/Shannon diversity) was reduced in treatment-naïve patients compared to siblings and patients in remission. Principal coordinate analysis using Bray–Curtis dissimilarity and UniFrac revealed microbial shifts in CD over the treatment course. In treatment-naïve PIBD, there was reduction in functional ability for amino acid metabolism and carbohydrate handling compared to controls (P = .038) and patients in remission (P = .027). Metabolic function returned to normal after remission was achieved. SCFA revealed consistent detection of lactate in treatment-naïve samples. This study adds in-depth 16S rRNA sequencing analysis on a small longitudinal cohort to the literature and includes sibling controls and patients with UC/IBD unclassified. It highlights the initial dysbiosis, reduced diversity, altered functional potential, and subsequent shifts in bacteria from diagnosis over time to remission.

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Accepted/In Press date: 4 June 2017
Published date: June 2017
Organisations: Human Genetics, Human Development & Health, Tissue Infection & Repair

Identifiers

Local EPrints ID: 411716
URI: http://eprints.soton.ac.uk/id/eprint/411716
ISSN: 1357-3039
PURE UUID: 39b8e414-5601-4e2f-b951-7ea3347c56bb
ORCID for David Cleary: ORCID iD orcid.org/0000-0003-4533-0700

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Date deposited: 22 Jun 2017 16:31
Last modified: 20 Sep 2017 16:31

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Contributors

Author: James J. Ashton
Author: Catherine M. Colquhoun
Author: David Cleary ORCID iD
Author: Tracy Coelho
Author: Rachel Haggarty
Author: Imke Mulder
Author: Akshay Batra
Author: Nadeem Afzal
Author: R. Mark Beattie
Author: Karen P. Scott
Author: Sarah Ennis

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