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Updated: May 13, 2026
Clinical Efficacy of Small Needle Knife Therapy on Stage I-II Frozen Shoulder
Published on: November 17, 2023
Association between 1400 metabolites mediated gut microbiota and frozen shoulder: An exploratory 2-step mendelian
Rong Shen1,2, Ji-Ang Li1,2, Han-Dan Xiao1,2,3
1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
None:
This study aimed to elucidate the causal relationship between gut microbiota (GM) and frozen shoulder (FS) and explore the potential mediating function of metabolites. Using pooled data from genome-wide association studies, we first performed bidirectional univariable Mendelian Randomization (MR) analysis to examine the relationship between GM and FS, avoiding any possible reverse causal influences. Exposure-related genetic variants that are independent of each other, were rigorously screened for use as instrumental variables. Further investigation of potential mediator pathways of the metabolites was conducted using a 2-step MR analysis. In this study, we primarily employ the inverse variance weighted method to assess the causal relationships among GM, metabolites, and FS, as well as to evaluate the potential mediating effect of metabolites. Heterogeneity and horizontal pleiotropy tests were conducted to assess the robustness of the results, such as MR-PRESSO, MR-Egger, Cochran Q. MR analysis identified 27 potential GM links associated with FS. In particular, 15 of them displayed positive associations with FS, while other microbiota showed negative associations. There was no significant correlation between GM and FS on reverse MR Analysis. Metabolites, including X-12844 levels, serve a mediating function in the development of FS. X-12844 levels mediate the effect of Eubacterium F sp000434115 on FS, with an indirect effect size of -0.016, accounting for 15.09% of the total effect size. For glycine to serine ratio, the mediation proportion was 8.19%. When examining 3-indoleglyoxylic acid levels, the mediating effect proportion is observed to be 11.66%. Our results provide evidence for a causal relationship between GM and FS as well as a metabolite-mediated pathway. These biomarkers may contribute to the detection, diagnosis, and treatment of FS, while providing fresh perspective on its underlying mechanism.
