The Preventive Effect Of Lactobacillus M5 On Osteoarthritis Induced By High Fat Diet In Mice

Osteoarthritis(OA)is a chronic degenerative joint disease mainly characterized by articular cartilage destruction,subchondral bone sclerosis,synovial membrane and surrounding tissue inflammation and the formation of varying degrees of osteophyte.There are many factors that affect the occurrence and development of OA.Obesity can accelerate the occurrence and development of OA through biomechanical and metabolic factors.Recent studies have shown that there is a strong relationship between the gut microbiota and obesity-related OA,but the exact relationship between them is not clear.Probiotics are a group of active beneficial microorganisms that can improve the host's microecological balance and play a beneficial role.The purpose of the present study was to evaluate the role of L.Paracasei subsp.paracasei M5(M5)in the prevention of OA caused by HFD and the relationship between gut microbiota and OA.Male Balb/c mice were fed either a control or high fat diet(HFD)from 8–20wks of age.Mice in the intervention group were given chondroitin sulfate(CS)and M5 alone or in combination with a HFD simultaneously.The results showed that M5 significantly reduced body weight,body fat index and Lee's index(P<0.05)in mice fed HFD.The results of organ index showed that M5 could significantly reduce the hepatomegaly and immune response caused by high-fat diet.The serum biochemical indicators were measured.The results showed that M5 could effectively reduce serum total cholesterol and triglyceride levels(P<0.05).In summary,M5 had a significant inhibitive effect on obesity caused by HFD.The relevant indicators of OA were measured.The results of HE staining and toluidine blue staining showed that the cartilage tissue was severely damaged by a HFD.In contrast,M5 could effectively increase the thickness of cartilage and the integrity of matrix staining.The results of determination of type ? collagen and type ? collagen C-terminal peptide content showed that HFD led to a decrease in type ? collagen and its degradation product type ? collagen C-terminal peptide content was significantly increased(P<0.05).M5 could effectively protect the destruction of type ? collagen.Adipokines in serum,infrapatellar fat pad(IPFP)and cartilage were measured.High-fat diets significantly increased serum,IPFP and cartilage leptin levels(P<0.05),and significantly decreased adiponectin levels(P<0.05).M5 significantly changed adipokines content in the serum and IPFP(P<0.05).In summary,high-fat diets lead to severe destruction of cartilage tissue and significant changes of adipokines in serum and IPFP.A HFD induced the development and progression of OA.M5 had a good preventive effect on HFD induced OA.High-throughput sequencing was used to analyze changes in gut microbiota.At the phylum level,high-fat diets significantly increased the abundance of Firmicutes and decreased the abundance of Bacteroidetes(P<0.05).Oral gavage administration of M5 and CS induced a much more significant increase in the abundance of Bacteroidetes and a far more notable decrease in the amount of Firmicutes.Further analysis at the genus level showed that the abundance of Bacteroides,Ruminococcaceae_UCG-014,Streptococcus,Ruminococcus_torques group and Lactococcus changes significantly among each group.There was a strong predictive relationship between the abundance of Ruminococcaceae_UCG-014,Streptococcus,Bacteroides and OA.In summary,M5 could prevent OA by regulating the gut microbiota.