Multi‐Omics Reveal the Dysregulated Gut‐Joint Axis in Knee Synovitis: Data from Two Osteoarthritis Studies in China

Gut microbiota dysbiosis and associated host immuno-metabolic disorders may play a role in knee synovitis. Herein, integrated multi-omics analyses of stool and blood samples from subjects from Pearl River Osteoarthritis Cohort (PROC, N = 207) are conducted to explore the potential gut-joint axis. Specifically, gut metagenomics, serum metabolomics and plasma proteomics are carried out. Knee synovitis is identified by magnetic resonance imaging. A total of 87 synovitis cases are identified in PROC, which are characterized by increased Firmicutes/Bacteroidetes (F/B) ratio. Alterations in microbial functions of both leucine and geraniol degradation are closely associated with increased serum 3-hydroxyisovaleric acid and decreased geranic acid. These perturbations are significantly correlated with F/B ratio and down-regulated plasma TWEAK. Building upon these, the potential synovial targets are explored using a synovial single-cell dataset and the Nanjing Osteoarthritis Cohort (NOC, N = 22). Synovial fluid proteomics, histological analysis, and in vitro experiments with human fibroblast-like synoviocytes (FLS) are conducted for NOC subjects with different synovitis grades. An upregulated TWEAK receptor is found in higher grade of synovitis. In vitro, higher TWEAK induced down-regulated TWEAK receptor in FLS. The study for the first time revealed the gut-joint axis in knee synovitis, providing new insight into potential targets for synovitis treatment.

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Publication Details

Journal
Advanced Science
Published
2025-12-07
DOI
https://doi.org/10.1002/advs.202512020
Primary Topic
Osteoarthritis Treatment and Mechanisms
Type
article
Field-Weighted Citation Impact
0.00

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article

Multi‐Omics Reveal the Dysregulated Gut‐Joint Axis in Knee Synovitis: Data from Two Osteoarthritis Studies in China

Zhihao Lu, Xiaolong Cao, Tianyu Chen, Changhai Ding et al.
Advanced Science
Osteoarthritis Treatment and Mechanisms
article

Multi‐Omics Reveal the Dysregulated Gut‐Joint Axis in Knee Synovitis: Data from Two Osteoarthritis Studies in China

Zhihao Lu, Xiaolong Cao, Tianyu Chen, Changhai Ding, Shixian Hu, Peihua Cao, Rocky S. Tuan, Zhaohua Zhu, Shangru Li, David John Hunter, Shengfa Li, Zhibo Wen, Jianzhao Ruan, Yi Liu, Jia Li, Zhong Alan Li, Jinhui Liu, Jiayuan Huang, Xiaoshuai Wang, Dongquan Shi, Jingyu Xie, Haitao Sun, Ziying Sun
article en

Abstract

Gut microbiota dysbiosis and associated host immuno-metabolic disorders may play a role in knee synovitis. Herein, integrated multi-omics analyses of stool and blood samples from subjects from Pearl River Osteoarthritis Cohort (PROC, N = 207) are conducted to explore the potential gut-joint axis. Specifically, gut metagenomics, serum metabolomics and plasma proteomics are carried out. Knee synovitis is identified by magnetic resonance imaging. A total of 87 synovitis cases are identified in PROC, which are characterized by increased Firmicutes/Bacteroidetes (F/B) ratio. Alterations in microbial functions of both leucine and geraniol degradation are closely associated with increased serum 3-hydroxyisovaleric acid and decreased geranic acid. These perturbations are significantly correlated with F/B ratio and down-regulated plasma TWEAK. Building upon these, the potential synovial targets are explored using a synovial single-cell dataset and the Nanjing Osteoarthritis Cohort (NOC, N = 22). Synovial fluid proteomics, histological analysis, and in vitro experiments with human fibroblast-like synoviocytes (FLS) are conducted for NOC subjects with different synovitis grades. An upregulated TWEAK receptor is found in higher grade of synovitis. In vitro, higher TWEAK induced down-regulated TWEAK receptor in FLS. The study for the first time revealed the gut-joint axis in knee synovitis, providing new insight into potential targets for synovitis treatment.

Advanced ScienceVol. 13(7)
University of Southern California (US), University of Tasmania (AU), Sun Yat-sen University (CN), Chinese University of Hong Kong (HK), Shenzhen University (CN), Royal North Shore Hospital (AU), Third Affiliated Hospital of Southern Medical University (CN), Third People's Hospital of Chengdu (CN), The Seventh Affiliated Hospital of Sun Yat-sen University (CN), Nanjing Drum Tower Hospital (CN), Institute for Musculoskeletal Health (AU), Zhujiang Hospital (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), Second Affiliated Hospital of Nanjing Medical University (CN), Sun Yat-sen University Cancer Center (CN), Beijing Tsinghua Chang Gung Hospital (CN), Southern Medical University (CN), Nanjing Medical University (CN), Chongqing Medical University (CN)
National Science Foundation, Arthritis Australia, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Innovation and Technology Commission, Chinese University of Hong Kong, Southern Medical University, National Health and Medical Research Council, National Key Research and Development Program of China, Basic and Applied Basic Research Foundation of Guangdong Province
Openalex Percentile: Top 45%
Osteoarthritis Treatment and Mechanisms
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