title: HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats.
abstract: The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m), compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Lin
authors.affiliation: Division of Rheumatology, University of Washington, VA Medical Center, Seattle, Washington, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Bach
authors.affiliation: Division of Rheumatology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Asquith
authors.affiliation: Moorfield's Eye Institute of London, London, United Kingdom.
authors.forename: Aaron Y
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Akileswaran
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Sean
authors.initials: S
authors.lastname: Davin
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Cambronne
authors.affiliation: Department of Rheumatology, University of Texas Southwestern, Dallas, Texas, United States of America.
authors.forename: Martha
authors.initials: M
authors.lastname: Dorris
authors.affiliation: University of Colorado Boulder, Boulder, Colorado, United States of America.
authors.forename: Justine W
authors.initials: JW
authors.lastname: Debelius
authors.affiliation: University of Colorado Boulder, Boulder, Colorado, United States of America.
authors.forename: Christian L
authors.initials: CL
authors.lastname: Lauber
authors.affiliation: University of Colorado Boulder, Boulder, Colorado, United States of America.
authors.forename: Gail
authors.initials: G
authors.lastname: Ackermann
authors.affiliation: University of Colorado Boulder, Boulder, Colorado, United States of America.
authors.forename: Yoshiki V
authors.initials: YV
authors.lastname: Baeza
authors.affiliation: Pediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Tejpal
authors.initials: T
authors.lastname: Gill
authors.affiliation: University of Colorado Boulder, Boulder, Colorado, United States of America; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado, United States of America.
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.affiliation: Pediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Colbert
authors.affiliation: Department of Rheumatology, University of Texas Southwestern, Dallas, Texas, United States of America.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Taurog
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Van Gelder
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Division of Rheumatology, Oregon Health & Science University, Portland, Oregon, United States of America; Dever's Eye Institute, Portland, Oregon, United States of America.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism / Q000382:microbiology*; D015796:HLA-B27 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D064307:Microbiota; D051381:Rats; D011917:Rats, Inbred Lew; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin