Can intestinal bacteria trigger rheumatological diseases?

What is this research project about?

Professor Witte (right) is talking with a patient.

What is this research project about?

Spondyloarthritis (SpA) is a group of frequent chronic rheumatological diseases which start in young adults and lead to disability of the patients. Current therapies are not efficient enough in stopping the progressive impairment of the musculoskeletal system. There is evidence that the microbiome of the gut is involved in triggering the disease. Clarifying the role of infections and the microbiome composition in the pathogenesis of SpA and its subform reactive arthritis may pave the way to new treatment modalities with better efficacy and less side effects.

What’s the current status?

With respect to a potential pathomechanism linking microbial colonization with autoimmunity and induction of SpA, it has been demonstrated that antibodies against Shigella flexneri, Klebsiella pneumoniae and Yersinia enterocolitica may crossreact with HLA-B27, the dominant genetic risk factor of SpA, and that antibodies against Klebsiella were found to be cytotoxic for cells expressing HLA-B27. Whether similar autoantibodies are induced by other members of the microbiota and if yes, under which conditions remains unresolved.

The image shows: Shigella flexneri (Shigellen), group of bacteria. Transmission electron microscopy, negative contrast. Scale = 1 μm. Source: Hans R. Gelderblom, Gabi Schlier, Rolf Reissbrodt/RKI

What are the project goals?

We want to identify alteration in the gut microbiota that are involved in triggering spondyloarthritis. Specifically we want to characterize dynamic microbiome  changes during the development and treatment of different forms of arthritis. Furthermore we want to identify antibodies associated with poor prognosis of SpA and members of the microbiome as well as antigens targeted by the immune system in arthritis patients. And our aim is to determine cross-reactivity between antibodies targeting microbial antigens and autoantigens develop intervention strategies to prevent the development of SpA and reactive arthritis.

How do we get there?

In the project RHEUMA-VOR we recruit a large number of patients from Lower Saxony with acute onset of SpA and control diseases. Stool, serum and DNA samples as well as PBMC and, when a joint aspiration was clinically indicated, synovial fluid (SF) and SF cells will be obtained and stored, and various disease-related clinical data as well as dietary habits will be collected. The patients from this inception cohort will be followed for > 2 years, and response to therapy, disease activity and disease progression will be monitored.

The photo shows Professor Strowig in his laboratory. © HZI/Waldthausen & Kreibig

Proctleaders

Project title: The microbiome – a trigger in arthritis? Linking alterations in microbiota composition to autoantibody development.

Prof. Dr. Alice McHardy

Projekt: B2, B10, C1

CV & Contact

Prof. Dr. Till Strowig

Projekte: B1, B2, RESIST-Kohorte

CV & Contact

Prof. Dr. Torsten Witte

Projekt: A2, B2

CV & Contact

Project B2 Publications

Publications of the Year 2020

Distinct Polysaccharide Utilization Determines Interspecies Competition between Intestinal Prevotella spp. Gálvez EJC, Iljazovic A, Amend L, Lesker TR, Renault T, Thiemann S, Hao L, Roy U, Gronow A, Charpentier E, Strowig T.  Cell Host Microbe. 2020 Dec 9;28(6):838-852.e6. doi: 10.1016/j.chom.2020.09.012. Epub 2020 Oct 27. PMID: 33113351.

Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels and Regulate Inflammation. Dürholz K, Hofmann J, Iljazovic A, Häger J, Lucas S, Sarter K, Strowig T, Bang H, Rech J, Schett G, Zaiss MM. Nutrients. 2020 Oct 20;12(10):3207. doi: 10.3390/nu12103207. PMID: 33092271; PMCID: PMC7589100.

The Role of Ames Dwarfism and Calorie Restriction on Gut Microbiota. Wiesenborn DS, Gálvez EJC, Spinel L, Victoria B, Allen B, Schneider A, Gesing A, Al-Regaiey KA, Strowig T, Schäfer KH, Masternak MM. J Gerontol A Biol Sci Med Sci. 2020 Jun 18;75(7):e1-e8. doi: 10.1093/gerona/glz236. PMID: 31665244; PMCID: PMC7302176.

Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation. Iljazovic A, Roy U, Gálvez EJC, Lesker TR, Zhao B, Gronow A, Amend L, Will SE, Hofmann JD, Pils MC, Schmidt-Hohagen K, Neumann-Schaal M, Strowig T. Mucosal Immunol. 2021 Jan;14(1):113-124. doi: 10.1038/s41385-020-0296-4. Epub 2020 May 20. PMID: 32433514; PMCID: PMC7790746.

Clinical, Radiological, and Laboratory Features of Spinal Cord Involvement in Primary Sjögren’s Syndrome. Butryn M, Neumann J, Rolfes L, Bartels C, Wattjes MP, Mahmoudi N, Seeliger T, Konen FF, Thiele T, Witte T, Meuth SG, Skripuletz T, Pawlitzki M. J Clin Med. 2020 May 14;9(5):1482. doi: 10.3390/jcm9051482. PMID: 32423153; PMCID: PMC7290729.

An Integrated Metagenome Catalog Reveals New Insights into the Murine Gut Microbiome. Lesker TR, Durairaj AC, Gálvez EJC, Lagkouvardos I, Baines JF, Clavel T, Sczyrba A, McHardy AC, Strowig T.  Cell Rep. 2020 Mar 3;30(9):2909-2922.e6. doi: 10.1016/j.celrep.2020.02.036. PMID: 32130896; PMCID: PMC7059117.

Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis; a longitudinal Swedish study. Do L, Granasen G, Hellman U, Lejon K, Geijer M, Baraliakos X, Witte T, Forsblad-d’Elia H. Rheumatology (Oxford) 2020

High frequency of variants in genes associated with primary immunodeficiencies in patients with rheumatic diseases with secondary hypogammaglobulinaemia Sogkas G, Dubrowinskaja N, Adriawan IR, Anim M, Witte T, Schmidt RE, Atschekzei F.  Ann Rheum Dis 2020

Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis; a longitudinal Swedish study. Do L, Granasen G, Hellman U, Lejon K, Geijer M, Baraliakos X, Witte T, Forsblad-d’Elia H. Rheumatology (Oxford) 2020

High frequency of variants in genes associated with primary immunodeficiencies in patients with rheumatic diseases with secondary hypogammaglobulinaemia Sogkas G, Dubrowinskaja N, Adriawan IR, Anim M, Witte T, Schmidt RE, Atschekzei F.  Ann Rheum Dis 2020

Project B2
Publications