Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients

Multiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the m...

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Main Authors: Matthew L. Stoll, Kimberly DeQuattro, Zhixiu Li, Henna Sawhney, Pamela F. Weiss, Peter A. Nigrovic, Tracey B. Wright, Kenneth Schikler, Barbara Edelheit, Casey D. Morrow, John D. Reveille, Matthew A. Brown, Lianne S. Gensler
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Children
Subjects:
Online Access:https://www.mdpi.com/2227-9067/9/4/569
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author Matthew L. Stoll
Kimberly DeQuattro
Zhixiu Li
Henna Sawhney
Pamela F. Weiss
Peter A. Nigrovic
Tracey B. Wright
Kenneth Schikler
Barbara Edelheit
Casey D. Morrow
John D. Reveille
Matthew A. Brown
Lianne S. Gensler
author_facet Matthew L. Stoll
Kimberly DeQuattro
Zhixiu Li
Henna Sawhney
Pamela F. Weiss
Peter A. Nigrovic
Tracey B. Wright
Kenneth Schikler
Barbara Edelheit
Casey D. Morrow
John D. Reveille
Matthew A. Brown
Lianne S. Gensler
author_sort Matthew L. Stoll
collection DOAJ
description Multiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the microbiota of HLA-B27+ pediatric offspring of ankylosing spondylitis (AS) patients with that of HLA-B27+ children with SpA. Human DNA was obtained from the offspring for determination of HLA-B27 status and polygenic risk score (PRS). Fecal specimens were collected from both groups for sequencing of the V4 region of the 16S ribosomal RNA gene. Among the offspring of AS patients, there was slight clustering by HLA-B27 status. After adjusting for multiple comparisons, five operational taxonomic units (OTUs) representing three unique taxa distinguished the HLA-B27+ from negative children: <i>Blautia</i> and <i>Coprococcus</i> were lower in the HLA-B27+ offspring, while <i>Faecalibacterium prausnitzii</i> was higher. HLA-B27+ offspring without arthritis were compared to children with treatment-naïve HLA-B27+ SpA. After adjustments, clustering by diagnosis was present. A total of 21 OTUs were significantly associated with diagnosis state, including <i>Bacteroides</i> (higher in SpA patients) and <i>F. prausnitzii</i> (higher in controls). Thus, our data confirmed associations with <i>B. fragilis</i> and <i>F. prausnitzii</i> with juvenile SpA, and also suggest that the mechanism by which HLA-B27 is associated with SpA may not involve alterations of the microbiota.
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spelling doaj.art-8f0249b457b24d179b7c7778a698cc6c2023-12-01T01:20:09ZengMDPI AGChildren2227-90672022-04-019456910.3390/children9040569Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis PatientsMatthew L. Stoll0Kimberly DeQuattro1Zhixiu Li2Henna Sawhney3Pamela F. Weiss4Peter A. Nigrovic5Tracey B. Wright6Kenneth Schikler7Barbara Edelheit8Casey D. Morrow9John D. Reveille10Matthew A. Brown11Lianne S. Gensler12Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, AL 35233, USADepartment of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, USACentre for Genomics and Personalized Health, Queensland University of Technology (QUT), Brisbane, QLD 4000, AustraliaDivision of Global Migration and Quarantine, Center for Disease Control, Washington, DC 30329, USADepartment of Pediatrics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADivision of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Boston, MA 02115, USADepartment of Pediatrics, University of Texas at Southwestern, Dallas, TX 75390, USADepartment of Pediatrics, University of Louisville, Louisville, KY 40292, USADepartment of Pediatrics, Connecticut Children’s Medical Center, Hartford, CT 06106, USADepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Internal Medicine, University of Texas at Houston, Houston, TX 77030, USAGenomics England, London EC1M 6BQ, UKDepartment of Medicine, Division of Rheumatology, University of California at San Francisco, San Francisco, CA 94143, USAMultiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the microbiota of HLA-B27+ pediatric offspring of ankylosing spondylitis (AS) patients with that of HLA-B27+ children with SpA. Human DNA was obtained from the offspring for determination of HLA-B27 status and polygenic risk score (PRS). Fecal specimens were collected from both groups for sequencing of the V4 region of the 16S ribosomal RNA gene. Among the offspring of AS patients, there was slight clustering by HLA-B27 status. After adjusting for multiple comparisons, five operational taxonomic units (OTUs) representing three unique taxa distinguished the HLA-B27+ from negative children: <i>Blautia</i> and <i>Coprococcus</i> were lower in the HLA-B27+ offspring, while <i>Faecalibacterium prausnitzii</i> was higher. HLA-B27+ offspring without arthritis were compared to children with treatment-naïve HLA-B27+ SpA. After adjustments, clustering by diagnosis was present. A total of 21 OTUs were significantly associated with diagnosis state, including <i>Bacteroides</i> (higher in SpA patients) and <i>F. prausnitzii</i> (higher in controls). Thus, our data confirmed associations with <i>B. fragilis</i> and <i>F. prausnitzii</i> with juvenile SpA, and also suggest that the mechanism by which HLA-B27 is associated with SpA may not involve alterations of the microbiota.https://www.mdpi.com/2227-9067/9/4/569HLA-B27microbiotaspondyloarthritis
spellingShingle Matthew L. Stoll
Kimberly DeQuattro
Zhixiu Li
Henna Sawhney
Pamela F. Weiss
Peter A. Nigrovic
Tracey B. Wright
Kenneth Schikler
Barbara Edelheit
Casey D. Morrow
John D. Reveille
Matthew A. Brown
Lianne S. Gensler
Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients
Children
HLA-B27
microbiota
spondyloarthritis
title Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients
title_full Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients
title_fullStr Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients
title_full_unstemmed Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients
title_short Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients
title_sort impact of hla b27 and disease status on the gut microbiome of the offspring of ankylosing spondylitis patients
topic HLA-B27
microbiota
spondyloarthritis
url https://www.mdpi.com/2227-9067/9/4/569
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