Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings

Charlotte R Hedin, Neil E McCarthy, Petra Louis, Freda M Farquharson, Sara McCartney, Kirstin Taylor, Natalie J Prescott, Trevor Murrells, Andrew J Stagg, Kevin Whelan, James O Lindsay

Research output: Contribution to journalArticle

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Abstract

Objective Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups.

Design Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip.

Results Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ2=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables.

Conclusions Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis.
Original languageEnglish
Pages (from-to)1578-1586
Number of pages9
JournalGut
Volume63
Issue number10
Early online date7 Jan 2014
DOIs
Publication statusPublished - Oct 2014

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Crohn Disease
Siblings
Blood Cells
T-Lymphocytes
Phenotype
Leukocyte L1 Antigen Complex
Dysbiosis
Permeability
Gastrointestinal Microbiome
Genotype
16S Ribosomal RNA
Lactulose
Rhamnose
Clostridium
Discriminant Analysis
Microbiology
Integrins
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction

Cite this

Hedin, C. R., McCarthy, N. E., Louis, P., Farquharson, F. M., McCartney, S., Taylor, K., ... Lindsay, J. O. (2014). Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings. Gut, 63(10), 1578-1586. https://doi.org/10.1136/gutjnl-2013-306226

Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings. / Hedin, Charlotte R; McCarthy, Neil E; Louis, Petra; Farquharson, Freda M; McCartney, Sara; Taylor, Kirstin; Prescott, Natalie J; Murrells, Trevor; Stagg, Andrew J; Whelan, Kevin; Lindsay, James O.

In: Gut, Vol. 63, No. 10, 10.2014, p. 1578-1586.

Research output: Contribution to journalArticle

Hedin, CR, McCarthy, NE, Louis, P, Farquharson, FM, McCartney, S, Taylor, K, Prescott, NJ, Murrells, T, Stagg, AJ, Whelan, K & Lindsay, JO 2014, 'Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings', Gut, vol. 63, no. 10, pp. 1578-1586. https://doi.org/10.1136/gutjnl-2013-306226
Hedin, Charlotte R ; McCarthy, Neil E ; Louis, Petra ; Farquharson, Freda M ; McCartney, Sara ; Taylor, Kirstin ; Prescott, Natalie J ; Murrells, Trevor ; Stagg, Andrew J ; Whelan, Kevin ; Lindsay, James O. / Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings. In: Gut. 2014 ; Vol. 63, No. 10. pp. 1578-1586.
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title = "Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings",
abstract = "Objective Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups.Design Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip.Results Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated na{\"i}ve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38{\%}) siblings compared with 2/25 (8{\%}) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ2=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables.Conclusions Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis.",
author = "Hedin, {Charlotte R} and McCarthy, {Neil E} and Petra Louis and Farquharson, {Freda M} and Sara McCartney and Kirstin Taylor and Prescott, {Natalie J} and Trevor Murrells and Stagg, {Andrew J} and Kevin Whelan and Lindsay, {James O}",
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TY - JOUR

T1 - Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings

AU - Hedin, Charlotte R

AU - McCarthy, Neil E

AU - Louis, Petra

AU - Farquharson, Freda M

AU - McCartney, Sara

AU - Taylor, Kirstin

AU - Prescott, Natalie J

AU - Murrells, Trevor

AU - Stagg, Andrew J

AU - Whelan, Kevin

AU - Lindsay, James O

N1 - Funding This research was funded by the charity Core.

PY - 2014/10

Y1 - 2014/10

N2 - Objective Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups.Design Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip.Results Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ2=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables.Conclusions Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis.

AB - Objective Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups.Design Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip.Results Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ2=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables.Conclusions Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis.

U2 - 10.1136/gutjnl-2013-306226

DO - 10.1136/gutjnl-2013-306226

M3 - Article

VL - 63

SP - 1578

EP - 1586

JO - Gut

JF - Gut

SN - 0017-5749

IS - 10

ER -