Microbes of the same order as the number of human cells inhabit the skin and mucosal surfaces inside and outside the body (1). It is now widely recognized that the host and the microbes coexist in close equilibrium and maintain a symbiotic relationship (1, 2). The intestinal tract contains the greatest diversity and density of microbial species, affecting many aspects of the host, including metabolism, circadian rhythm, neurobehavioral development, and immune defenses to pathogens (2). It is also well known that the interaction between host and microbes is necessary for the proper development of the host immune system (2, 3). For example, germ-free animals have defects in the development of gut-associated lymphoid tissue and Peyer’s patches, formation of a tight junction between intestinal epithelial cells, and secretion of antimicrobial peptides and mucus from epithelial cells (2). Many microbiota, so-called symbionts, have regulatory properties beneficial to the host and prevent colonization by the pathogens, while some microbiota, called pathobionts, induce a proinflammatory state, triggering disease under certain circumstances (2). Intestinal dysbiosis, a state of microbial imbalance, has been implicated in the pathogenesis of a number of diseases, particularly autoimmune disorders in which the host immune system erroneously attacks its own tissues (2, 4). As expected, intestinal dysbiosis in inflammatory bowel disease is characterized by its reduced diversity and, in contrast, increased number of pathobionts (2). Intriguingly, the disturbance of intestinal microbiota can influence the onset and/or progression of autoimmune diseases including rheumatoid arthritis (RA), even though it is localized to tissues far removed from the gut (4, 5). RA is a prototype chronic inflammatory disorder characterized by uncontrolled inflammation of synovial tissue, leading to joint destruction and a wide array of multisystem comorbidities (4). Its pathogenesis is thought to be attributed to complex interplay between multiple genes and diverse environmental factors, including infectious microorganisms (5–7). Interestingly, antibiotic treatment or germ-free conditions interrupted the development of arthritis in several experimental RA models with diverse genetic predispositions, such as zymosan-treated SKG mice, interleukin-1 (IL-1) receptor antagonist–knockout mice, T cell receptor–transgenic K/BxN mice, and HLA–B27–transgenic rats (5). Conversely, arthritis symptoms developed in animals that were housed under germ-free conditions and were colonized with specific bacteria, such as Lactobacillus bifidus and segmented filamentous bacteria, and recolonized with feces from other sources (5). Thus, it has now been speculated that the microbiota may become one of the missing links in the pathogenesis of RA. Over the past few decades, diverse pathogens, including some bacteria (eg, Escherichia coli, Streptococcus, and Mycoplasma), viruses (eg, Parvovirus and Retrovirus), and mycobacterium have been suggested as possible causative agents in RA (6). Moreover, recent studies have shown a close correlation between peptidylarginine deiminase produced by gingival pathogens and the development and