Effects of probiotics on joint homeostasis and osteoarthritis: Development of microbe-gut-cartilage axis-on-a-chip
12 affiliations
- 1Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China.
- 2InnoHK Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China.
- 3Department of Orthopedic Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
- 4Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
- 5Department of Rehabilitation Medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
- 6Institute of Digestive Disease and Department of Medicine and Therapeutics, The State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
- 7Clinical Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
- 8Clinical Research Centre, Beijing Tsinghua Changgung Hospital, Tsinghua Medicine, Tsinghua University, Beijing, China.
- 9School of Biomedical Engineering, Tsinghua Medicine, Tsinghua University, Beijing, China.
- 10Institute for Tissue Engineering and Regenerative Medicine, and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
- 11Peter Hung Pain Research Institute, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
- 12The State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
Abstract
Although emerging evidence implicates gut microbiome-cartilage cross-talk in the pathogenesis of osteoarthritis (OA), the most common joint disease, studying this microbe-gut-joint axis remains challenging due to limitations of animal models and conventional in vitro systems. Here, we report a microbe-gut-cartilage axis-on-a-chip (MGCAoC) that recreates tissue-specific microenvironments with oxygen gradients and physiological fluid shear. The computer simulation-optimized chip design generates an anoxic-oxic interface for the gut module and enables perfusion of probiotic metabolites to human cartilage organoids without cross-contamination. Multiomics profiling suggested that probiotic metabolites may promote cartilage anabolism, potentially involving PI3K and MAPK pathway, and this effect was associated with up-regulated collagen type II and aggrecan expression while suppressing metalloproteinases. In inflamed cartilage organoids, these metabolites were associated with reduced proinflammatory signaling while preserving matrix integrity. The chondroprotective effects were confirmed using cartilage organoids derived from patients with OA treated with identified metabolites. This MGCAoC enables mechanistic investigation of gut-joint axis physiology and provides a versatile preclinical tool for screening probiotic-based OA therapeutics.
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BibTeX
@article{liu2026effects,
title = {{Effects of probiotics on joint homeostasis and osteoarthritis: Development of microbe-gut-cartilage axis-on-a-chip}},
author = {Jun Liu and Ning Zhang and Yiting Lei and Xiaoshuai Wang and Xiang Zhang and Wei Huang and Changhai Ding and Denghui Xie and Jun Yu and Rocky S. Tuan and Zhong Alan Li},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeg8557},
url = {https://www.science.org/doi/10.1126/sciadv.aeg8557},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Effects of probiotics on joint homeostasis and osteoarthritis: Development of microbe-gut-cartilage axis-on-a-chip
AU - Jun Liu
AU - Ning Zhang
AU - Yiting Lei
AU - Xiaoshuai Wang
AU - Xiang Zhang
AU - Wei Huang
AU - Changhai Ding
AU - Denghui Xie
AU - Jun Yu
AU - Rocky S. Tuan
AU - Zhong Alan Li
PY - 2026
DA - 2026/10/09
JO - Science Advances
DO - 10.1126/sciadv.aeg8557
UR - https://www.science.org/doi/10.1126/sciadv.aeg8557
AB - Although emerging evidence implicates gut microbiome-cartilage cross-talk in the pathogenesis of osteoarthritis (OA), the most common joint disease, studying this microbe-gut-joint axis remains challenging due to limitations of animal models and conventional in vitro systems. Here, we report a microbe-gut-cartilage axis-on-a-chip (MGCAoC) that recreates tissue-specific microenvironments with oxygen gradients and physiological fluid shear. The computer simulation-optimized chip design generates an anoxic-oxic interface for the gut module and enables perfusion of probiotic metabolites to human cartilage organoids without cross-contamination. Multiomics profiling suggested that probiotic metabolites may promote cartilage anabolism, potentially involving PI3K and MAPK pathway, and this effect was associated with up-regulated collagen type II and aggrecan expression while suppressing metalloproteinases. In inflamed cartilage organoids, these metabolites were associated with reduced proinflammatory signaling while preserving matrix integrity. The chondroprotective effects were confirmed using cartilage organoids derived from patients with OA treated with identified metabolites. This MGCAoC enables mechanistic investigation of gut-joint axis physiology and provides a versatile preclinical tool for screening probiotic-based OA therapeutics.
SN - 2375-2548
ER -