Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis

Abstract

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.

A systematic review of the association between fibromyalgia and functional gastrointestinal disorders

“…While we did not seek to explore FGIDs in other rheumatic or musculoskeletal conditions, these groups are often used in comparison to fibromyalgia. Interestingly, we found higher rates of IBS in subjects with other rheumatological conditions compared to healthy controls further supporting an interaction between the gut microbiota and the musculoskeletal system (66,67). Sperber et al (32) reported that fibromyalgics with IBS had worse symptoms of fatigue, morning tiredness and pain, compared to those without IBS.…”

Gut–Joint Axis: The Role of Physical Exercise on Gut Microbiota Modulation in Older People with Osteoarthritis

“…This correlation has been described in rodent models and humans affected by OA and is characterized by increased levels of circulatory inflammatory markers including bacterially produced lipopolysaccharides (LPS) [36,37], suggesting that microbiome-derived proinflammatory metabolites could play a putative role in OA pathogenesis. Moreover, it has recently been shown that the subchondral dysbiosis resulting from the bacterial translocation from GM to the joint, might support the development of OA [14]. Therefore, considering gut dysbiosis and the leaky gut syndrome as cofactors in the development of inflammaging and consequently of OA [38], it is likely to hypothesize the existence of a 'gut-joint axis' [7,[14][15][16]].…”

“…Moreover, it has recently been shown that the subchondral dysbiosis resulting from the bacterial translocation from GM to the joint, might support the development of OA [14]. Therefore, considering gut dysbiosis and the leaky gut syndrome as cofactors in the development of inflammaging and consequently of OA [38], it is likely to hypothesize the existence of a 'gut-joint axis' [7,[14][15][16]].…”

“…Several studies [14][15][16] have hypothesized the linkage between GM and osteoarthritis, taking into account the potential correlations between serum levels of bacterial metabolites and joint degeneration, however, at present, no systematic reviews have clearly described this topic.…”

Shea Nut Oil Extracts Enhance the Intra-Articular Sodium Hyaluronate Effectiveness on Surgically Induced OA Progression in Rats

“…Moreover, an emerging concept of gut-joint axis has associated the gut dysbiosis (perturbation of gut microbiota (GM) biodiversity and function), and the leaky gut syndrome with the joint disease progression [42,43]. In both human and rodent model, an increase in serum level of the pro-inflammatory marker and bacterial metabolites were associated with OA severity [44,45].…”