Gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice

Abstract

Gut microbiota dysbiosis has been studied under the pathological conditions of osteoarthritis (OA). However, the effect of antibiotic-induced gut flora dysbiosis on OA remains incompletely understood at present. Herein, we used a mouse (8 weeks) OA model of destabilization of the medial meniscus (DMM) and gut microbiome dysbiosis induced by antibiotic treatment with ampicillin and neomycin for 8 weeks. The results show that antibiotic-induced intestinal microbiota dysbiosis reduced the serum level of lipopolysaccharide (LPS) and the inflammatory response, such as suppression of the levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can lead to decreased matrix metalloprotease-13 (MMP-13) expression and improvement of OA after joint injury. In addition, trabecular thickness (Tb.Th) and osteophyte scores were increased significantly in antibiotic-induced male mice compared with female mice. We further used network correlation analysis to verify the effect of gut microbiota dysbiosis on OA. Therefore, this study contributes to our understanding of the gut-joint axis in OA and reveals the relationship between the inflammatory response, sex and gut microbiota, which may provide new strategies to prevent the symptoms and long-term sequelae of OA.

Taxonomic changes in the gut microbiota are associated with cartilage damage independent of adiposity, high fat diet, and joint injury

“…Furthermore, antibiotic treatment prior to injury has been shown to mitigate OA caused by a loading-induced injury 25 , as well as in toll-like receptor 5 knockout mice that are protected from metabolic syndrome 26 . Antibiotic-induced dysbiosis from treatment with ampicillin and neomycin reduced serum levels of LPS and improved OA outcomes after injury 27 , further illustrating that ablation of certain microbes could be a viable preventative treatment strategy for cartilage damage. Associations between the gut microbiome, muscle quality 28 , and bone strength 29 , contributors to OA pathogenesis 30 , have also been identified, suggesting that modulating the microbiome could have broad protective applications on the joint organ system.…”

The relation between the gut microbiome and osteoarthritis: A systematic review of literature

“…prevalence are probably able to dysregulate the delicate balance of pro-inflammatory markers [ 34 ]. However, two of the studies we included in our analysis [ 36 , 37 ], reported that gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice. Additionally, an antibiotic-induced gut microbiota dysbiosis in OA male mice significantly decreased the relative abundance of Bacteroidetes, but for female mice, the relative abundance of Firmicutes was increased significantly compared with that in Con-OA female mice [ 37 ].…”

“…However, two of the studies we included in our analysis [ 36 , 37 ], reported that gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice. Additionally, an antibiotic-induced gut microbiota dysbiosis in OA male mice significantly decreased the relative abundance of Bacteroidetes, but for female mice, the relative abundance of Firmicutes was increased significantly compared with that in Con-OA female mice [ 37 ]. While this further highlights the pivotal role of the microbiota as whole in the development, progression and symptomatology of OA, also induces contradictory conclusion about bacterial diversity and F/B ratio.…”

Gut-Bone Axis: A Non-Negligible Contributor to Periodontitis

“…Transplantation of fecal materials from metabolic syndrome patients in GF mice enhanced gut permeability by downregulating TJ proteins ZO-1 and occludin, causing elevated plasma level of LPS and subsequently exacerbated OA severity ( Huang et al., 2020 ). Antibiotic treatment altered gut microbiota and decreased serum LPS level, alleviating circulating inflammation and preventing OA progression ( Guan et al., 2020 ). Estrogen-deficient mice exhibited pathological bone loss and impaired bone microarchitecture in femur, with downregulated gut epithelial TJ protein expression and increased serum endotoxin levels, and these pathologies could be prevented by probiotics administration ( Li J. Y. et al., 2016 ).…”