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Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis
  1. Jean-Marie Berthelot1,
  2. Jérémie Sellam2,3,4,
  3. Yves Maugars1 and
  4. Francis Berenbaum2,3,4
  1. 1Rheumatology Unit, Nantes University Hospital, CHU Nantes, 44093 Nantes Cedex 01, France
  2. 2Sorbonne University, Paris, France
  3. 3INSERM UMRS_938, CRSA, Paris, France
  4. 4Department of Rheumatology, Assistance Publique - Hôpitaux de Paris (AP-HP), Saint- Antoine Hospital, DMU 3iD, Paris, France
  1. Correspondence to Dr Jean-Marie Berthelot; jeanmarie.berthelot{at}


DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance.

  • osteoarthritis
  • chondrocytes
  • infections

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  • Contributors JMB wrote the first draft of this review, which was extensively reorganised and improved by the other authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data is avaible in a public, open access repository.

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