Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis


Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = −0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler’s Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9–4.1 vs. 3.9 mm, IQR 3.6–4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3–5.5 vs. 4.1 mm, IQR 3.9–4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. 1.

    Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, et al. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther.2014;16:486.

    Article  Google Scholar 

  2. 2.

    Tejesvi MV, Arvonen M, Kangas SM, Keskitalo PL, Pirttila AM, Karttunen TJ, et al. Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis. 2016;35:363–70.

    CAS  Article  Google Scholar 

  3. 3.

    Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 2016;68:2646–61.

    CAS  Article  Google Scholar 

  4. 4.

    Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015;67:128–39.

    CAS  Article  Google Scholar 

  5. 5.

    Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt 5):1469–76.

    CAS  Article  Google Scholar 

  6. 6.

    Stoll ML, Cron RQ. The microbiota in pediatric rheumatic disease: epiphenomenon or therapeutic target? Curr Opin Rheumatol. 2016;28:537–43.

    CAS  Article  Google Scholar 

  7. 7.

    Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010;32:815–27.

    CAS  Article  Google Scholar 

  8. 8.

    Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, et al. The toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011;332:974–7.

    CAS  Article  Google Scholar 

  9. 9.

    Dewhirst FE, Chien CC, Paster BJ, Ericson RL, Orcutt RP, Schauer DB, et al. Phylogeny of the defined murine microbiota: altered Schaedler flora. Appl Environ Microbiol. 1999;65:3287–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Gomes-Neto JC, Mantz S, Held K, Sinha R, Segura Munoz RR, Schmaltz R, et al. A real-time PCR assay for accurate quantification of the individual members of the altered Schaedler Flora microbiota in gnotobiotic mice. J Microbiol Methods. 2017;135:52–62.

    CAS  Article  Google Scholar 

  11. 11.

    Kumar R, Maynard CL, Eipers P, Goldsmith KT, Ptacek T, Grubbs JA, et al. Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile. BMC Microbiol. 2016;16:5.

    Article  Google Scholar 

  12. 12.

    Arrieta MC, Walter J, Finlay BB. Human microbiota-associated mice: a model with challenges. Cell Host Microbe. 2016;19:575–8.

    CAS  Article  Google Scholar 

  13. 13.

    Asquith MJ, Stauffer P, Davin S, Mitchell C, Lin P, Rosenbaum JT. Perturbed mucosal immunity and dysbiosis accompany clinical disease in a rat model of spondyloarthritis. Arthritis Rheumatol. 2016;68:2151–62.

    CAS  Article  Google Scholar 

  14. 14.

    Johansson ME. Mucus layers in inflammatory bowel disease. Inflamm Bowel Dis. 2014;20:2124–31.

    Article  Google Scholar 

  15. 15.

    Grigg JB, Sonnenberg GF. Host-microbiota interactions shape local and systemic inflammatory diseases. J Immunol. 2017;198:564–71.

    CAS  Article  Google Scholar 

  16. 16.

    Ganesh BP, Klopfleisch R, Loh G, Blaut M. Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella typhimurium-infected gnotobiotic mice. PLOS One. 2013;8:e74963.

    CAS  Article  Google Scholar 

  17. 17.

    Michail S, Durbin M, Turner D, Griffiths AM, Mack DR, Hyams J, et al. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis. 2012;18:1799–808.

    Article  Google Scholar 

  18. 18.

    Papa E, Docktor M, Smillie C, Weber S, Preheim SP, Gevers D, et al. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease. PLOS One. 2012;7:e39242.

    CAS  Article  Google Scholar 

  19. 19.

    Shah R, Cope JL, Nagy-Szakal D, Dowd S, Versalovic J, Hollister EB, et al. Composition and function of the pediatric colonic mucosal microbiome in untreated patients with ulcerative colitis. Gut Microbes. 2016;7:384–96.

    CAS  Article  Google Scholar 

  20. 20.

    Picco P, Gattorno M, Marchese N, Vignola S, Sormani MP, Barabino A, et al. Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol. 2000;18:773–8.

    CAS  PubMed  Google Scholar 

  21. 21.

    Martinez-Gonzalez O, Cantero-Hinojosa J, Paule-Sastre P, Gomez-Magan JC, Salvatierra-Rios D. Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives. Br J Rheumatol. 1994;33:644–7.

    CAS  Article  Google Scholar 

  22. 22.

    Faith JJ, Ahern PP, Ridaura VK, Cheng J, Gordon JI. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Transl Med. 2014;6:220ra11.

    Article  Google Scholar 

  23. 23.

    Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390–2.

    PubMed  Google Scholar 

  24. 24.

    Cary SG, Blair EB. New transport medium for shipment of clinical specimens. I. Fecal specimens. J Bacteriol. 1964;88:96–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Monach PA, Mathis D, Benoist C. The K/BxN arthritis model. Curr Protoc Immunol. 2008;15:22. ChapterUnit 15

    PubMed  Google Scholar 

  26. 26.

    Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Lozupone CA, Turnbaugh PJ, et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc Natl Acad Sci USA. 2011;108:4516–22. Suppl 1

    CAS  Article  Google Scholar 

Download references


This work was supported by funding from the NIH/NIEHS (1R21ES024413-01; PI Dr. Stoll), NIH/NIAMS (P60 AR064172), the American College of Rheumatology (PI Dr. Stoll), and the Childhood Arthritis Rheumatology Research Alliance (PI Dr. Stoll). The following are acknowledged for their support of the Microbiome Resource at the University of Alabama at Birmingham: Comprehensive the Cancer Center (P30AR050948), the Center for Clinical Translational Science (UL1TR001417), the University Wide Institutional Core and the Heflin Center for Genomic Sciences.

Author information



Corresponding author

Correspondence to Matthew L Stoll.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Stoll, M.L., Pierce, M.K., Watkins, J.A. et al. Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis. Genes Immun 20, 158–166 (2019).

Download citation

Further reading


Quick links