title: The Influence of the Autoimmunity-Associated Ancestral HLA Haplotype AH8.1 on the Human Gut Microbiota: A Cross-Sectional Study.
abstract: Multiple immune-related genes are encoded in the HLA complex on chromosome 6p21. The 8.1 ancestral haplotype (AH8.1) include the classical HLA alleles HLA-B*08:01 and HLA-DRB1*03:01, and has been associated with a large number of autoimmune diseases, but the underlying mechanisms for this association are largely unknown. Given the recently established links between the gut microbiota and inflammatory diseases, we hypothesized that the AH8.1 influences the host gut microbial community composition. To study this further, healthy individuals were selected from the Norwegian Bone Marrow Donor Registry and categorized as either I. AH8.1 homozygote (n=34), II. AH8.1 heterozygote (n=38), III. Non AH8.1 heterozygote or IV. HLA-DRB1 homozygote but non AH8.1 (n=15). Bacterial DNA from stool samples were subjected to sequencing of the V3-V5 region of the 16S rRNA gene on the 454 Life Sciences platform and data analyzed using Mothur and QIIME. The results showed that the abundances of different taxa were highly variable within all pre-defined AH8.1 genotype groups. Using univariate non-parametric statistics, there were no differences regarding alpha or beta diversity between AH8.1 carriers (categories I and II) and non-carriers (categories III and IV), however four different taxa (Prevotellaceae, Clostridium XVIII, Coprococcus, Enterorhabdus) had nominally significant lower abundances in AH8.1 carriers than non-carriers. After including possible confounders in a multivariate linear regression, only the two latter genera remained significantly associated. In conclusion, the overall contribution of the AH8.1 haplotype to the variation in gut microbiota profile of stool in the present study was small.
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine and K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Hov
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanzi
authors.initials: H
authors.lastname: Zhong
authors.affiliation: BGI-Shenzhen, Shenzhen, China; Shanghai Majorbio Bio-pharm Technology Co. Ltd., Shanghai, China.
authors.forename: Bingcai
authors.initials: B
authors.lastname: Qin
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Jarl Andreas
authors.initials: JA
authors.lastname: Anmarkrud
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Holm
authors.affiliation: Christian-Albrechts-University of Kiel, Institute of Clinical Molecular Biology, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Institute of Clinical Medicine and K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine and K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
mesh_terms: D000328:Adult; D015551:Autoimmunity; D001419:Bacteria / Q000145:classification / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D010802:Phylogeny
chemical_list: D059811:HLA-DRB1 Chains; D006649:Histocompatibility Antigens