The causal role of gut microbiota in development of osteoarthritis

Objective: There is considerable evidence for relationship between gut microbiota and osteoarthritis (OA), but no studies have investigated their causal relationship. Method: This study utilized large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and OA risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for OA. Comprehensively sensitive analyses were performed to validate the robustness of results and novel multivariable MR analyses were further conducted to ensure the independence of causal association. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. Finally, enrichment analyses were used to investigate the biofunction. Results: After correction, three microbial taxa were identified to be causally associated with diverse joint OA (P-FDR < 0.100), namely Methanobacteriaceae family for knee OA (P-FDR = 0.043) and any OA (P-FDR = 0.028), Desulfovibrionales order forkneeOA(P-FDR = 0.045) andRuminiclostridium5 genus forkneeOA(P-FDR = 0.063). In addition, we also identified five suggestive microbial taxa thatwere significant with three different methods under the nominal significance (P < 0.05). Sensitive analysis excluded the influence of heterogeneity and horizontal pleiotropy andmultivariable MR analysis ruled out the possibility of horizontal pleiotropy of BMI. GO enrichment analysis illustrates the protective mechanism of the identified taxa against OA. Conclusions: This study found that several microbial taxa were causally associated with diverse joint OA. The results enhanced our understanding of gut microbiota in the pathology of OA. (c) 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study identified several microbial taxa that were causally associated with different types of OA, enhancing our understanding of the role of gut microbiota in the pathology of OA.