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Patient-derived Enterococcus faecium with inflammatory genotypes promote colitis

  • Original Article—Alimentary Tract
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Abstract

Background

Dysbiosis of gut microbiota promotes colitis in ulcerative colitis (UC). Enterococcus faecium is an important constituent of dysbiotic microbiota. However, the mechanisms underlying E. faecium-induced colitis remain unclear.

Methods

Overall, 23 E. faecium strains isolated from human feces and 3 commercial strains were inoculated into Il10−/− mice. Mouse colons were histologically evaluated and analyzed using real-time PCR analysis of cytokines. Genes in 26 E. faecium strains were identified by whole-genome shotgun sequencing of genomic DNA. The production of reactive oxygen species (ROS) from each strain was measured. An antioxidant, lipoic acid, was orally administered to the colitis mouse model.

Results

Inoculation of E. faecium derived from patients with UC resulted in colitis in Il10−/− mice. The genotypes of 26 strains were characterized by identifying 1893 known genes; clustering all the strains based on the genotypes showed two major groups—inflammatory and probiotic clusters. Additionally, linear discriminant analysis clarified that lipoic acid metabolism was a significantly abundant pathway in the probiotic cluster compared to the inflammatory cluster. Further, the production of ROS was greater in inflammatory than in probiotic strains. Administration of lipoic acid in E. faecium-inoculated mice ameliorated colitis.

Conclusions

Enterococcus faecium strains in the inflammatory cluster promoted colitis with higher production of ROS than the strains in the probiotic cluster.

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Acknowledgements

The authors thank Ms. Akiko Katayama (Kanazawa University) and Katsumi Hara for assistance with histological analysis; Ms. Maki Wakabayashi (Kanazawa University) for animal care. We thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

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Author notes

  1. Ziyu Wang and Noriho Iida contributed equally.

Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Ziyu Wang, Noriho Iida, Jun Seishima, Hirofumi Okafuji, Eishiro Mizukoshi & Shuichi Kaneko

  2. Department of Bacteriology, Graduate School of Medicinal Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, Japan

    Masahiro Yutani & Yukako Fu**aga

  3. Department of Bacteriology, Graduate School of Medicine, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, Japan

    Yusuke Hashimoto & Haruyoshi Tomita

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  1. Ziyu Wang
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Correspondence to Eishiro Mizukoshi.

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Wang, Z., Iida, N., Seishima, J. et al. Patient-derived Enterococcus faecium with inflammatory genotypes promote colitis. J Gastroenterol 57, 770–783 (2022). https://doi.org/10.1007/s00535-022-01905-4

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  • DOI: https://doi.org/10.1007/s00535-022-01905-4

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