Researchers from Peking Union Medical College Hospital, Beijing, in collaboration with BGI genomics, complete the oral and intestinal microbial genome research on rheumatoid arthritis (RA). The results show that the gut and oral microbiome are involved in the pathophysiology of RA and provide indication for developing microbiome-assisted personalized treatments. The latest finding was published online on July 27th, 2015, in Nature Medicine.
RA is an autoimmune disease with high disability rate, and the number of patients is as high as tens of millions of patients worldwide. RA has been considered to be related to bacterial infections. However, little is known about the possible involvement of bacteria and if they participate as causative or protective agents. In addition, although methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs) can ease the disease, they can not completely cure RA, and may have serious side effects. Therefore, a comprehensive understanding of the RA related microbial flora may expand our understanding of the pathophysiology of RA, and help to promote early diagnosis and precise medical treatment. In this study, professor Xuan Zhang from Peking Union Medical College Hospital,Beijing and collaborator from BGI genomics, collected plaque, saliva and faecal samples from treatment-naïve RA patients, with samples from healthy people as controls(including immediate relatives and unrelated relatives), using meta-genome shotgun sequencing to detect microbial DNA, and comparing changes of oral and intestinal microflora before and after treatment with DMARDs.
Though there have been reports about the relationship between the intestinal flora and Type II diabetes and the colorectal cancer, it is the first time that the mechanism of both the oral and intestinal microbial flora are investigated simultaneously in one of human major chronic non-infectious diseases. Dr. Dongya Zhang, a major participant of this project, introduces that Haemophilus sp. in patients with RA is relatively depleted, and inversely correlates with autoimmune antibody titer in RA, whereas Lactobacillus salivarius in the plaque, saliva and faeces of RA patients is significantly enriched, especially in patients with high disease activity.
Functional convergence is also observed--the RA gut and oral microbiomes show abnormalities in the redox environment, iron, sulfur, zinc and arginine transport and metabolism, and possible molecular mimicry to RA-related human antigens, suggesting that this flora abnormalities has an important role in the pathophysiology of RA, and may be directly involved in the disease.
In addition, based on the metagenomics analysis of the relationship between the oral and the intestinal microbial population, the researchers constructed a classification model to differentiate RA patients from healthy subjects. The accurate rate of the diagnosis can be increased to nearly 100% using this classification model in all three parts. The classification model based on the analysis of the meta genomic association can also help to determine the efficacy of DMARDs. In RA patients reaching remission after an effective treatment, their metagenome restored to that similar to the microbial flora of healthy subjects. The study also implicates that oral and intestinal metagenomic analysis could also be useful to distinguish different stages of disease and evaluate patient’s response to treatment effect, and is helpful in disease stratification and prediction of drug efficacy.
Professor Xuan Zhang from Peking Union Medical College Hospital, the leading investigator of this project, said this is for the first time metagenomics analysis is performed on both oral and intestinal microbial flora, and reveal its potential role in the development of one of human major chronic non-infectious diseases and its clinical implication. Further clinical verification will expand our understanding of the pathogenesis of RA. We expect the metagenome-wide association study will be helpful in promoting patient stratification, predicting drug efficacy and exploring novel therapeutic target, leading to precise diagnosis and treatment of RA.