On July 7, Prof. Ning Kang's team of Huazhong University of Science and Technology, Prof. Han Jinxiang’s team of Shandong First Medical University, and Prof. Zhang Lei's team of Shandong University published cooperative research in the international top gastrointestinal journal Gut online, The paper is entitled "A hidden link in gut joint axis: gut microbes promote rheumatoid arthritis at early stage by enhancing ascorbate degradation". The co-first authors of this paper are Dr. Zhao Yan and Dr. Cheng Mingyue. Among them, Cheng Mingyue is a PhD student in bioinformatics major of HUST. Co-corresponding authors are Prof. Zhang Lei, Prof. Ning Kang, and Prof. Han Jinxiang.
Rheumatoid arthritis (RA) is a chronic, autoimmune, and inflammatory disease. The number of RA patients in China is increasing year by year. Clinical studies have shown that RA patients are usually ascorbate (Vitamin C) deficient. As a powerful antioxidant, Vitamin C can inhibit the pro-inflammatory factors that promoting arthritis progression. In addition, Vitamin C is also involved in the synthesis of collagen, which is the main protein of joint tissue and bone. Therefore, in clinical treatment, RA patients require high-dose supplementation to maintain an acceptable plasma level of Vitamin C, so as to relieve pain, protect cartilage, and relieve autoimmune reaction.Gut microbiome play a key regulatory role in human health and disease, and are closely related to host metabolism and immune function. Studies have shown that gut microbiome are associated with the induction of autoimmune diseases, such as rheumatoid arthritis. However, in the course of rheumatoid arthritis, especially in the process of vitamin C supplement treatment, whether and how gut microbiome play a role is an unresolved problem.
Through integrating multi-omics datasets including gut metagenomics, inflammatory cytokines level, and metabolites of blood and knee-joint synovial fluid of RA patients, this study demonstrates that gut microbiome could promote RA progression via enhancing ascorbate degradation, and provides a potential approach to prevent the development of arthritis through interfering gut-joint axis. In RA patients, the vitamin C degradation function of gut microbiome is significantly higher than that in healthy people, accompanied by increasing level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). IL-6 and TNF-α are clinically used as the target site for the RA treatment. Moreover, this study found that Escherichia coli and Streptococcus bovis are the key driving microbes of this gut-joint axis, especially in the early stage of RA.
The provided reservoir of the potential microbiome-metabolites-arthritis links in this study can be used as a reference for future clinical trials.
This study was funded by National Natural Science Foundation of China, Academic Promotion Project of Shandong First Medical University, and Ministry of Science and Technology’s National Key Research and Development Program.
Article link:
https://gut.bmj.com/content/early/2021/07/07/gutjnl-2021-325209
