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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Nutritional Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1444892
This article is part of the Research Topic The Nutritional Immunological Effects and Mechanisms of Extracts and Metabolites Based on the Homology of Medicine and Food - Volume II View all 5 articles

Impact of Dysregulated Microbiota-derived C18 Polyunsaturated Fatty Acid Metabolites on Arthritis Severity in Mice with Collagen-induced Arthritis

Provisionally accepted
Katsuhiko Yoneda Katsuhiko Yoneda 1Sho Sendo Sho Sendo 1Takaichi Okano Takaichi Okano 1Hidenori Shimizu Hidenori Shimizu 2Hirotaka Yamada Hirotaka Yamada 1Keisuke Nishimura Keisuke Nishimura 1Yo Ueda Yo Ueda 1Jun Saegusa Jun Saegusa 1*
  • 1 Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan
  • 2 Noster Inc, Kyoto, Kyōto, Japan

The final, formatted version of the article will be published soon.

    Objective. We aimed to evaluate microbiome and microbiota-derived C18 dietary polyunsaturated fatty acids (PUFAs), such as conjugated linoleic acid (CLA), and to investigate their differences that correlate with arthritis severity in collagen-induced arthritis (CIA) mice. Methods. On day 84 after induction, during the chronic phase of arthritis, cecal samples were analyzed using 16S rRNA sequencing, and plasma and cecal digesta were evaluated using liquid chromatography-tandem mass spectrometry. Differences in microbial composition between 10 control (Ctrl) and 29 CIA mice or between the mild and severe subgroups based on arthritis scores were identified. The cecal metabolite profile and its correlation with the microbiome were evaluated with respect to arthritis severity. Results. Hydroxy and oxo metabolite levels were higher in CIA mice than in Ctrl mice, some of which, including 10-hydroxy-cis-6-18:1, were positively correlated with arthritis scores. The 9-trans,11-trans CLA levels in CIA mice had a negative linear correlation with arthritis scores. Microbial diversity was lower in severe CIA mice than in mild CIA or Ctrl mice. The abundance of Lactobacillus relatively increased in the severe subgroup of CIA mice compared with that in the mild subgroup and was positively correlated with arthritis severity. Conclusion. Alterations in gut microbiota and microbiota-derived C18 PUFA metabolites are associated in CIA mice and correlated with arthritis scores, indicating that plasma or fecal C18 PUFA metabolites can be potential biomarkers for arthritis severity and dysbiosis.

    Keywords: Metabolome, Rheumatoid arthritis, 16S rRNA, collagen-induced arthritis, polyunsaturated fatty acids, gut microbiota-derived metabolites

    Received: 06 Jun 2024; Accepted: 09 Dec 2024.

    Copyright: © 2024 Yoneda, Sendo, Okano, Shimizu, Yamada, Nishimura, Ueda and Saegusa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jun Saegusa, Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan

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