ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 54

A Metagenome-wide Association Study of Gut Microbiome Revealed Novel Etiology of Rheumatoid Arthritis in the Japanese Population

Toshihiro Kishikawa 1, Yuichi Maeda 2, Takuro Nii 1, Daisuke Motooka 1, Yuki Matsumoto 1, Masato Matsushita 3, Hidetoshi Matsuoka 4, Maiko Yoshimura 4, Shoji Kawada 5, Satoru Teshigawara 4, Eri Oguro 1, Yasutaka Okita 4, Keisuke Kawamoto 5, Shinji Higa 6, Toru Hirano 7, Masashi Narazaki 1, Atsushi Ogata 5, Yukihiko Saeki 8, Shota Nakamura 1, Hidenori Inohara 1, Atsushi Kumanogoh 1, Kiyoshi Takeda 1 and Yukinori Okada1, 1Osaka University, Suita, Japan, 2Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan, 3Saiseikai Senri Hospital, Suita, Japan, 4NHO Osaka Minami Medical Center, Kawachinagano, Japan, 5Daini Osaka Police Hospital, Tennoji-ku, Japan, 6Osaka Second Police Hospital, Osaka, Japan, 7Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan, 8NHO Osaka Minami Medical Center, Kawachinagano, Osaka, Japan

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ,

Session Information

Date: Sunday, November 10, 2019

Title: RA – Etiology & Pathogenesis Poster I

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: 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 (ncase = 82, ncontrol = 42) by utilizing 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 (but other than previously reported Prevotella copri) 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 was significantly decreased in the RA metagenome compared to 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 (GWAS) 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 etiology.

Phylogenetic tree. Levels L2–L7 are from the inside layer to the outside layer. The size and color of dots represent relative abundance and effect sizes, respectively. The 12 clades with significant case–control associations -q < 0.05- are outlined in red.

Disclosure: T. Kishikawa, None; Y. Maeda, Bristol-Myers Squibb Company, 8, Chugai Pharmaceutical Co. Ltd, 8, Eli Lily, 8, Mitsubishi-Tanabe, 8, Pfizer, 8; T. Nii, None; D. Motooka, None; Y. Matsumoto, None; M. Matsushita, None; H. Matsuoka, None; M. Yoshimura, None; S. Kawada, None; S. Teshigawara, None; E. Oguro, None; Y. Okita, None; K. Kawamoto, None; S. Higa, None; T. Hirano, None; M. Narazaki, None; A. Ogata, None; Y. Saeki, None; S. Nakamura, None; H. Inohara, None; A. Kumanogoh, None; K. Takeda, None; Y. Okada, None.

To cite this abstract in AMA style:

Kishikawa T, Maeda Y, Nii T, Motooka D, Matsumoto Y, Matsushita M, Matsuoka H, Yoshimura M, Kawada S, Teshigawara S, Oguro E, Okita Y, Kawamoto K, Higa S, Hirano T, Narazaki M, Ogata A, Saeki Y, Nakamura S, Inohara H, Kumanogoh A, Takeda K, Okada Y. A Metagenome-wide Association Study of Gut Microbiome Revealed Novel Etiology of Rheumatoid Arthritis in the Japanese Population [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/a-metagenome-wide-association-study-of-gut-microbiome-revealed-novel-etiology-of-rheumatoid-arthritis-in-the-japanese-population/. Accessed .

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