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  2. BzATP reverses ferroptosis-induced gut microbiota disorders in collagen-induced arthritis mice

BzATP reverses ferroptosis-induced gut microbiota disorders in collagen-induced arthritis mice

  • Int Immunopharmacol. 2023 Sep 13;124(Pt A):110885. doi: 10.1016/j.intimp.2023.110885.
Yeye Ma 1 Wenjing Li 1 Sijia Niu 1 Xiaoying Zhu 1 Maolin Chu 2 Weiyan Wang 1 Wentian Sun 1 Xuemin Wei 1 Juan Zhang 3 Zhiyi Zhang 4
Affiliations

Affiliations

  • 1 Department of Rheumatology, The First Affiliated Hospital, Harbin Medical University, 23 Youzheng St., Nan Gang District, Harbin, China.
  • 2 Department of Urology, The Second Affiliated Hospital, Harbin Medical University, Nan Gang District, Harbin, China.
  • 3 Department of Rheumatology, The First Affiliated Hospital, Harbin Medical University, 23 Youzheng St., Nan Gang District, Harbin, China. Electronic address: zhangjuan3732@hrbmu.edu.cn.
  • 4 Department of Rheumatology, The First Affiliated Hospital, Harbin Medical University, 23 Youzheng St., Nan Gang District, Harbin, China. Electronic address: zhangzhiyi@hrbmu.edu.cn.
Abstract

Recent studies suggested that altered gut microbiota may be related to the pathogenesis of rheumatoid arthritis (RA), albeit the exact mechanisms are unknown. In this study, we aimed to discover the particular mechanism of RA treatment by microbiota by investigating the effects of Ferroptosis on gut microbiota and its metabolites in collagen-induced arthritis (CIA) mice. Mice were divided into five groups: control, CIA, erastin, BzATP, and BzATP + erastin group. We performed 16S rDNA Sequencing and metabolomics analysis on mouse feces and found that erastin and BzATP altered the microbiota and metabolites. The findings demonstrated that the microbiota was significantly disturbed at the phylum (Proteobacteria, Firmicutes, and Bacteroidota) and genus level (Lachnospiraceae_NK4A136, Lactobacillus, and Bifidobacterium) in the CIA group, and erastin exacerbated this disturbance. Unexpectedly, BzATP treatment could repair the disruptive effects of erastin. Additionally, there were significant variations in metabolites between each group. Erastin worsened metabolite abnormalities in CIA mice, while BzATP mitigated them, consistent with the microbiota results. These findings provide novel perspectives and insights into the therapy of RA.

Keywords

BzATP; Ferroptosis; Gut microbiota; Metabolites; Rheumatoid arthritis.

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