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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Systems Microbiology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1427195

The effect of gut microbiome and plasma metabolome on systemic sclerosis: A bidirectional Two-sample Mendelian Randomization Study

Provisionally accepted
Qiming Meng Qiming Meng 1,2*Shasha Xie Shasha Xie 1,2Lin Wang Lin Wang 3*
  • 1 Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • 3 The First Hospital of Changsha, Changsha, Hunan Province, China

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

    Background Cellular and molecular biology, combined with research on the human microbiome and metabolome, have provided new insights into the pathogenesis of systemic sclerosis (SSc). However, most studies on gut microbiota (GM) and metabolome in SSc are observational studies. The impact of confounding factors and reverse causation leads to different insights. To shed light on this matter, we utilized Mendelian randomization (MR) to determine the causal effect of GM/metabolites on SSc.Based on summary-level data from genome-wide association studies, bidirectional Two-sample MR was conducted involving 196 GM, 1400 plasma metabolism, and 9095 SSc. Inverse Variance Weighting (IVW) was mainly used for effect estimation.Results Forward MR analysis found that three GM and two plasma metabolites are causally related to SSc. IVW results showed Victivallaceae (family) (OR, 1.469; 95%CI, 1.099-1.963; P=0.009) and LachnospiraceaeUCG004 (genus) (OR, 1.548; 95%CI, 1.020-2.349; P=0.04) were risk factor of SSc. Conversely, Prevotella7 (genus) (OR, 0.759; 95%CI, 0.578-0.997; P=0.048)was a protective factor of SSc. The results on plasma metabolites indicated that Pregnenediol disulfate (C21H34O8S2) levels(OR, 1.164; 95%CI, 1.006-1.347; p=0.041)was a risk factor of SSc, while Sphingomyelin (d18:1/19:0, d19:1/18:0) levels (OR, 0.821; 95%CI, 0.677-0.996; P=0.045)was a protective factor of SSc. Reverse MR analysis did not find causally relationship between SSc and the above GM/plasma metabolites.Our results revealed the causally effect between GM/plasma metabolites and SSc. These findings provided new insights into the mechanism of SSc. In particular, we demonstrated Prevotella7 was a protective factor of SSc despite its controversial role in SSc in previous researches.

    Keywords: systemic sclerosis, Gut Microbiota, Plasma metabolites, Mendelian randomization, causally effect

    Received: 11 May 2024; Accepted: 04 Jul 2024.

    Copyright: © 2024 Meng, Xie and Wang. 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:
    Qiming Meng, Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    Lin Wang, The First Hospital of Changsha, Changsha, 410005, Hunan Province, China

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