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A high-fiber diet synergizes with Prevotella copri and exacerbates rheumatoid arthritis

Cellular & Molecular Immunology volume 19, pages 1414–1424 (2022)Cite this article

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Abstract

Both preclinical and established rheumatoid arthritis (RA) patients display alterations in the gut microbiome. Prevotella spp. are preferentially enriched in a subset of RA patients. Here, we isolated a Prevotella strain, P. copri RA, from the feces of RA patients and showed that colonization of P. copri RA exacerbated arthritis in a collagen-induced arthritis (CIA) model. With the presence of P. copri RA colonization, a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation. Colonization of P. copri together with a high-fiber diet enabled the digestion of complex fiber, which led to the overproduction of organic acids, including fumarate, succinate and short-chain fatty acids. Succinate promoted proinflammatory responses in macrophages, and supplementation with succinate exacerbated arthritis in the CIA model. Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.

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Data availability

The genome sequences and RNA sequence data produced in this study are available at the Sequence Read Archive of the National Center for Biotechnology Information (the accession numbers for the sequences reported in this paper are NCBI SRA: SRR14576269).

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Acknowledgements

We thank all donors who participated in this study.

Funding

This work was supported by the National Natural Science Foundation of China (81788101, 82230060, 81630064, and 81701624), the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-017, 2021-I2M-1-047, 2021-I2M-1-040, and 2021-I2M-1-016), the Capital’s Funds for Health Improvement and Research (2020-2-4019) and the National Key Research and Development Program of China (Grant no. 2018YFE0207300).

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Author notes

  1. These authors contributed equally: Lingjuan Jiang, Mengmeng Shang, Shengnan Yu.

Authors and Affiliations

  1. Department of Medical Research Center, National Science and Technology Key Infrastructure on Translational Medicine, Peking Union Medical College Hospital; Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Lingjuan Jiang, Mengmeng Shang & Tingting Wang

  2. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Lingjuan Jiang, Mengmeng Shang, Shengnan Yu & Tingting Wang

  3. Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Yudong Liu, Min Wang & Xuan Zhang

  4. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Hui Zhang

  5. Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Yangzhong Zhou

  6. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Hui Li

  7. Institute for Immunology, School of Medicine, Tsinghua University, Beijing, 100084, China

    Zhihua Liu

  8. Tsinghua-Peking Center for Life Sciences, Beijing, 100084, China

    Zhihua Liu

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Contributions

Conception and design of the study: LJJ, ZHL, and XZ; implementation of in vivo and in vitro experiments: LJJ, MMS and SNY; analysis of 16 S rRNA sequencing data and the transcriptome data analysis: LJJ; statistical analysis: MMS and HZ; critical comments: YDL, YZZ, MW, TTW, XZ and ZHL; drafting of manuscript: LJJ and SNY; final approval of the version of the article to be published: all authors.

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Correspondence to Zhihua Liu or Xuan Zhang.

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All studies reported here were approved by the Institutional Review Board and Animal Care and Use Committee of Peking Union Medical College Hospital (PUMCH).

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Jiang, L., Shang, M., Yu, S. et al. A high-fiber diet synergizes with Prevotella copri and exacerbates rheumatoid arthritis. Cell Mol Immunol 19, 1414–1424 (2022). https://doi.org/10.1038/s41423-022-00934-6

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