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Effect of the gut microbiota on frozen shoulder and potential mediating role of inflammatory cytokines: A Mendelian randomization study and mediation analysis

Year: 2025
Type: article
Study design: Observational Study
Abstract: Frozen shoulder (FS), characterized by chronic inflammation and joint fibrosis, remains etiologically unclear. Emerging evidence suggests that gut microbiota may modulate systemic inflammation via the "gut-joint axis," yet causal links to FS are unverified. This study aimed to investigate GM-FS causality using Mendelian randomization and explore inflammatory cytokines as potential mediators. This study was conducted using genome-wide association study data from MiBioGen and IEU. Six cytokines were included in the mediation analysis. Inverse variance weighted served as the primary method, supplemented by weighted median and MR-Egger, with sensitivity analyses to ensure robustness. Among 119 bacterial genera, Butyrivibrio (OR = 0.922), Lachnospiraceae UCG004 (OR = 0.897), Lactobacillus (OR = 0.843), Parabacteroides (OR = 0.790), and Ruminococcaceae UCG003 (OR = 0.836) are protective against FS, while Eubacterium coprostanoligenes (OR = 1.172) is a risk factor (all P < .05). Mediation analysis revealed interferon -γ partially mediated the protective effect of Lactobacillus on FS (β = 0.170, P = .011). These findings advance the "gut-joint axis" theory and suggest novel therapeutic targets for FS, deserving further experimental validation.
Source: Medicine
Authors: Zhiyun Feng, Xiule Fang, Tao Ding
Language: English
Open Access status: gold
Estimated APC paid: $1,950
OpenAlex ID: W4414669641
FWCI:
Cites: 57
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