Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice.

Published

Journal Article

OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage. METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability. RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1β, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations. CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.

Full Text

Duke Authors

Cited Authors

  • Huang, Z; Chen, J; Li, B; Zeng, B; Chou, C-H; Zheng, X; Xie, J; Li, H; Hao, Y; Chen, G; Pei, F; Shen, B; Kraus, VB; Wei, H; Zhou, X; Cheng, L

Published Date

  • May 2020

Published In

Volume / Issue

  • 79 / 5

Start / End Page

  • 646 - 656

PubMed ID

  • 32205337

Pubmed Central ID

  • 32205337

Electronic International Standard Serial Number (EISSN)

  • 1468-2060

Digital Object Identifier (DOI)

  • 10.1136/annrheumdis-2019-216471

Language

  • eng

Conference Location

  • England