After persevering in the unpopular field of osteoarthritis research for 25 years, Professor Guanghua Lei’s team from Xiangya Hospital of Central South University finally achieved a significant breakthrough. Recently, in collaboration with the team led by the researcher Cen Xie from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, they published their research findings in the journal Science, providing the first evidence that osteoarthritis is closely related to intestinal dysbiosis and proposing an innovative “gut-joint axis” pathogenic mechanism. This research not only overturns the traditional understanding, but also discovers that the old drug “Ursodeoxycholic Acid (UDCA)” has the potential to treat osteoarthritis, bringing new hope for its treatment.

A decisive choice made 25 years ago

Looking back on this achievement, Guanghua Lei believes that the choice of research direction 25 years ago is particularly crucial.

In the late 1990s, most researchers focus on hot fields, while he firmly selected osteoarthritis field, a less appreciated research direction. “When there are multiple treatment methods for a certain disease but with limited efficacy, it implies that its pathogenesis remains incompletely defined.” Guanghua Lei is well aware that only by understanding the essence of the disease can we truly benefit patients.

Facing the numerous challenges in the research of osteoarthritis-significant differences between animal models and human bodies, complex molecular mechanisms, and significant individual variations in treatment responses, Guanghua Lei did not back down. He innovatively proposed a “Clinical-Basic-Translational” full-chain research model, and determined to solve this medical problem at its root.

A decade of persistence in the remote mountains

To obtain reliable data, the research team delved into Longshan County in Western Hunan, a poor county in the Wuling Mountain area, and established the “Xiangya Osteoarthritis Study (XO Study)” cohort. The reason for choosing this place is straightforward: the local residents have a high joint load and a low migration rate, and “the impoverished area is in urgent need of high-quality medical resources”-meeting the demands of scientific research while also serving the people.

Since 2013, the follow-up team with over 20 members has taken two physical examination coaches every winter to the mountainous areas of Western Hunan for over 2 months. They provided detailed checks for over 4,000 residents. This decade-long persistence has finally accumulated valuable research data.

Unveiling the mechanism of “gut-joint axis”

Through analyzing mass data, the team found the Glycoursodeoxycholic acid (GUDCA) level in the blood is negatively correlated with the severity degree of osteoarthritis. This unexpected discovery made the team extremely excited.

The subsequent research discovered that the number of Clostridium butyricum in the intestines of osteoarthritis patients has decreased, leading to sufficient “maintenance cost” GUDCA synthesis, and thereby impacting joint repair.

Guanghua Lei vividly illustrated this mechanism as “the intestinal defector causing the collective layoff of the “repair workers” in the joints”.

What’s even more astonishing is that the team found the drug UDCA for cholelithiasis can simulate the effect of GUDCA, which can significantly improve osteoarthritis in animal models.

The treatment prospect of using old drugs in new ways

“Using old drugs in new ways has the advantages of low cost and short period”. Guanghua Lei said that UDCA has been approved for hepatobiliary disease, and its safety has been fully verified. The team is planning to conduct clinical trials. If the therapeutic effect is confirmed, they will quickly revise the clinical guidelines.

This research has not only brought new hope for osteoarthritis treatment, but also displayed the value of persisting innovative exploration. As Guanghua Lei said, “unlocking the mysteries of diseases requires systematic, full-chain research and, even more importantly, the perseverance to sit on a “cold bench” for extended periods.” With the clarification of “gut-joint axis” mechanism, the medical community’s understanding of osteoarthritis and its treatment strategies may undergo a fundamental transformation.