A research team led by Professor Alan Li Zhong, Vice-Chancellor Assistant Professor in the Department of Biomedical Engineering (BME) at The Chinese University of Hong Kong (CUHK), has developed a first-of-it-kind “microbe-gut-cartilage axis-on-a-chip” (MGCAoC). This tiny, human cell-based platform mimics how gut microbes influence joint health, revealing how specific probiotics and their metabolites promote cartilage growth and reduce joint inflammation. The findings offer new hope for treating osteoarthritis and have been published in the prestigious international journal Science Advances. Overcoming the limitations of traditional animal and laboratory models Osteoarthritis is one of the most common joint diseases in the world, causing chronic pain, stiffness and reduced mobility, often severely impacting patients’ quality of life. Current treatments mainly manage symptoms, with very few options able to stop the disease from worsening. Beyond aiding digestion, gut microbes also produce small molecules that can affect the immune system and inflammation throughout the body. Researchers have therefore investigated whether gut microbes may influence joints and play a role in the development or progression of osteoarthritis. However, tests on animals often fail to accurately replicate how the human body actually works. At the same time, standard laboratory culture dishes cannot keep gut bacteria and joint cells alive together because they require completely different living conditions. As a result, directly studying the gut-joint connection has remained a major challenge. A human chip model that rebuilds the gut-cartilage connection To address this challenge, the research team developed the first microfluidic platform that integrates gut microbes, intestinal epithelium and human cartilage organoids in a single system. The chip was carefully engineered to create an anoxic-oxic interface that supports probiotic growth, while also providing fluid flow conditions that more closely resemble those in the human body. Importantly, it allows certain probiotic metabolites produced on the gut side to reach the cartilage side without unwanted cross-contamination. In other words, the chip acts like a tiny and controllable human-inspired model, allowing researchers to observe how gut microbes affect cartilage in real time. Probiotics linked to healthier joint cartilage Using this platform, the researchers introduced specific probiotics into the gut module and studied how the cartilage organoids responded. They found that probiotic-related signals were associated with improved cartilage development. The cartilage organoids showed higher levels of key anabolic markers, including collagen type II and aggrecan, while molecules linked to tissue breakdown were reduced. The team further tested the system under inflammatory conditions relevant to osteoarthritis. Even in this pro-inflammatory environment, probiotic-derived signals were associated with lower inflammatory responses and better preservation of cartilage structure. These findings suggest that specific probiotics may have a protective effect on joint cartilage. Study reveals possible biological mechanisms To better understand how these effects occur, the team carried out multi-omics analyses and identified several candidate metabolites and signalling pathways that may mediate communication between gut microbes and cartilage. The results suggest that the beneficial effects of probiotics and their metabolites may be linked to important signalling pathways, such as PI3K/AKT and MAPK/ERK, which are known to regulate cell growth, tissue development and inflammatory responses. Further experiments using cartilage organoids derived from osteoarthritis patients demonstrated that certain probiotic-derived metabolites could reduce inflammatory and degenerative markers, supporting their therapeutic potential and providing a foundation for developing more targeted therapies with fewer adverse effects. Opening new avenues for osteoarthritis therapies Professor Li said: “This study is the first to establish an in vitro human model of the microbe-gut-cartilage axis. It provides researchers with a new way to directly investigate the causal relationship between gut microbes and joint health in a controlled setting. Beyond helping scientists better understand osteoarthritis, the platform could also be used in the future to screen probiotics, functional metabolites and other microbiome-based treatment strategies. The team believes this work may help open a new avenue for osteoarthritis research, one that starts from the gut to protect the joints.” |
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