16s rRNA from fecal pellets of lipodystrophic and wild-type mice fed high fat or chow diet

Objective: Lipodystrophic mice are protected from cartilage damage following joint injury. This protection can be reversed by the implantation of a small adipose tissue graft. The purpose of this study was to evaluate the relationship between the gut microbiota and knee cartilage damage while controlling for adiposity, high fat diet, and joint injury using lipodystrophic (LD) mice.Methods: LD and littermate control (WT) mice were given a high fat diet, chow diet, or were rescued with fat implantation, then challenged with destabilization of the medial meniscus surgery to induce osteoarthritis (OA). Serum and synovial fluid lipopolysaccharide (LPS) were measured. 16s rRNA sequencing was conducted on feces. MaAslin2 was used to determine associations between taxonomic relative abundance and OA severity measured by Modified Mankin Score.Results: While serum LPS levels between groups were similar, synovial fluid LPS levels were increased in both limbs of HFD WT mice compared to all groups, except for fat transplanted animals. The Bacteroidetes:Firmicutes ratio of the gut microbiota was significantly reduced in HFD and OA-rescued animals when compared to chow. Nine significant associations were found between gut microbiota taxa and Modified Mankin Score.Conclusions: Key taxonomic changes in the gut microbiota are associated with cartilage damage when controlling for obesogenic diet and adipose tissue. Manipulation of these taxa in future studies will be used to understand causal relationships between alterations in the gut microbiome and cartilage health.