Mediation Analysis Of Gut Microbiota And Potential Treatment Strategy For Metabolic Associated Osteoarthritis

Objectives:The aims of this study were(1)to identify the core gut microbiota associated with osteoarthritis based on a large population-level database and to test whether the core gut microbiota mediated the link between metabolic syndrome along with its components and osteoarthritis.(2)To determine whether metformin use associated with a reduced risk of total knee replacement and knee pain in diabetic and/or obese patients with knee osteoarthritisMethods:For chapter one,whether gut microbiota mediated the link between metabolic syndrome and osteoarthritis,we first excluded 824 participants with missing values of age,sex,body mass index(BMI),location,Bristol stool type,marital status,education status,occupation type and medication use from the Guangdong Gut Microbiota Project(n=7009)and screened 6185 individuals who were further divided into osteoarthritis group(n=1099)and non-osteoarthritis group(n=5086).Multivariable association linear model(MaAsLin)was used to adjust for the above covariates and to identify gut microbiota significantly associated with osteoarthritis.Osteoarthritisrelated microbial index(OMI)was calculated by coefficient,P value and microbial abundance to detect the mediation effect of gut microbiota on the association between metabolic syndrome along with its components and osteoarthritis.Chapter two examined whether the use of metformin among diabetes and/or obese patients combined with knee osteoarthritis associated with reduced risk of total knee replacement and lower degree of knee pain.We firstly selected participants with both knee osteoarthritis and diabetes and/or obese from the local hospital information system of Zhujiang Hospital,Southern Medical University(n=879).Eligible patients were divided into metformin group and non-metformin group.After that,univariate and multivariate regression models and inverse probability treatment weighting(IPTW)models were used to evaluate the relationship between metformin use and the risk of knee arthroplasty as well as the degree of knee pain.Furthermore,we analysed the association between duration of metformin use(<1 year VS>= 1 year)and risk of total knee arthroplasty as well as degree of knee pain.Results:In this study,participants in osteoarthritis group were older and had a higher proportion of females and greater BMI.Regarding metabolic components,participants in osteoarthritis group had a significantly higher prevalence of metabolic syndromes(Mets)and type 2 diabetes(T2DM),higher waist circumference,blood presure and blood glucose,lower density lipoprotein and triglyceride.We also found that the diversity of faecal microbiota decreased significantly in patients with osteoarthritis,with a total of 52 microbes associated with osteoarthritis.These 52 microbes partly mediate the effects of Mets and its components on osteoarthritis.In diabetic and/or obese patients with knee osteoarthritis,metformin users had a higher rate of analgesics.Metformin use was significantly associated with a lower risk of knee arthroplasty and a significantly lower degree of knee pain.Meanwhile,increased duration of metformin use was significantly associated with reduced severity of knee pain.Conclusions:The main conclusions of this study are as follows:(1)Gut microbiota may partially mediate the association of metabolic syndrome and its components with osteoarthritis.(2)In diabetic and/or obese patients with knee osteoarthritis,metformin use may reduce the risk of total knee arthroplasty and improve knee symptoms.