TY - JOUR T1 - Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis DO - 10.1136/annrheumdis-2019-215743 SP - annrheumdis-2019-215743 AU - Toshihiro Kishikawa AU - Yuichi Maeda AU - Takuro Nii AU - Daisuke Motooka AU - Yuki Matsumoto AU - Masato Matsushita AU - Hidetoshi Matsuoka AU - Maiko Yoshimura AU - Shoji Kawada AU - Satoru Teshigawara AU - Eri Oguro AU - Yasutaka Okita AU - Keisuke Kawamoto AU - Shinji Higa AU - Toru Hirano AU - Masashi Narazaki AU - Atsushi Ogata AU - Yukihiko Saeki AU - Shota Nakamura AU - Hidenori Inohara AU - Atsushi Kumanogoh AU - Kiyoshi Takeda AU - Yukinori Okada Y1 - 2019/11/02 UR - http://ard.bmj.com/content/early/2019/11/01/annrheumdis-2019-215743.abstract N2 - Objective The causality and pathogenic mechanism of microbiome composition remain elusive in many diseases, including autoimmune diseases such as rheumatoid arthritis (RA). This study aimed to elucidate gut microbiome’s role in RA pathology by a comprehensive metagenome-wide association study (MWAS).Methods We conducted MWAS of the RA gut microbiome in the Japanese population (n case=82, n control=42) by using whole-genome shotgun sequencing of high depth (average 13 Gb per sample). Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis and pathway analysis).Results Phylogenetic case–control association tests showed high abundance of multiple species belonging to the genus Prevotella (e.g., Prevotella denticola) in the RA case metagenome. The non-linear machine learning method efficiently deconvoluted the case–control phylogenetic discrepancy. Gene functional assessments showed that the abundance of one redox reaction-related gene (R6FCZ7) was significantly decreased in the RA metagenome compared with controls. A variety of biological pathways including those related to metabolism (e.g., fatty acid biosynthesis and glycosaminoglycan degradation) were enriched in the case–control comparison. A population-specific link between the metagenome and host genome was identified by comparing biological pathway enrichment between the RA metagenome and the RA genome-wide association study results. No apparent discrepancy in alpha or beta diversities of metagenome was found between RA cases and controls.Conclusion Our shotgun sequencing-based MWAS highlights a novel link among the gut microbiome, host genome and pathology of RA, which contributes to our understanding of the microbiome’s role in RA aetiology. ER -