Distinct murine cartilage microbial DNA signatures are seen in high fat diet-induced obesity and aging

Abstract

density (BMD), trabecular volume (BV/TV, %) and thickness (Tb.Th/mm) of subchondral bone. Microorganisms-derived shortchain fatty acids, like butyric acid, caproic acid, and caprylic acid, etc. were significantly decreased in age mice, whereas long-chain fatty acid levels were higher than young mice. Microbiome profiles of 28 families of microorganisms were significantly altered in aged mice. Of them, microorganisms related to probiotics, like Lactobacillacea, were reduced, whereas bacteria relevant to metabolic syndrome, like Lachnospiraceae, were upregulated. In vitro, butyrate treatment attenuated extracellular matrix proteoglycan underproduction and aggrecan expression loss in inflamed chondrocytes, as well as ameliorated mineralized matrix accumulation and osteogenic gene expression in inflamed osteoblasts. Conclusions: Gut microbiome is correlated with age-mediated articular cartilage and subchondral bone loss. Dysbiosis alters shortchain fatty acid metabolism, which is important to stabilize extracellular matrix production in chondrocytes and osteoblasts to sustain cartilage and subchondral bone integrity. This study offers a productive insight into the communication of gut microbiome to host chondrocytes and osteoblasts in the development of joint degeneration. Control of short-chain fatty acid metabolism in joint microenvironment has the perspective of remedial effects to ameliorate age-induced joint damage.