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

Abstract

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.

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Acknowledgements

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.

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Correspondence to Matthew L Stoll.

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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). https://doi.org/10.1038/s41435-018-0024-1

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