Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1437869

Causal Pathways in Lymphoid leukaemia: The Gut Microbiota, Immune Cells, and Serum Metabolites

Provisionally accepted
Xin Zhuang Xin Zhuang 1Rong Yang Rong Yang 1*Xiaoying Man Xiaoying Man 1*Ruochen Wang Ruochen Wang 1*Yifen Shi Yifen Shi 1,2,3*
  • 1 First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • 2 Qinghai Province Women and Children's Hospital, Xining, Qinghai Province, China
  • 3 Zhejiang Provincial Clinical Research Center For Hematological disorders, Wenzhou, China

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

    Background：We employed Mendelian randomization (MR) to investigate the causal relationship between the gut microbiota and lymphoid leukaemia, further exploring the causal relationships among immune cells, lymphoid leukaemia, and potential metabolic mediators. Methods：We utilized data from the largest genome-wide association studies to date, encompassing 418 species of gut microbiota, 713 types of immune cells, and 1,400 serum metabolites as exposures. Summary statistics for lymphoid leukaemia, acute lymphocytic leukaemia (ALL), and chronic lymphocytic leukaemia (CLL) were obtained from the FinnGen database. We performed bidirectional Mendelian analyses to explore the causal relationships among the gut microbiota, immune cells, serum metabolites, and lymphoid leukaemia. Additionally, we conducted a two-step mediation analysis to identify potential intermediary metabolites between immune cells and lymphoid leukaemia. Results：Several gut microbiota were found to have causal relationships with lymphoid leukaemia, ALL, and CLL, particularly within the Firmicutes and Bacteroidetes phyla. In the two-step MR analysis, various steroid hormone metabolites (such as DHEAS, pregnenolone sulfateprogestogen derivatives, and androstenediol-related compounds) were identified as potential intermediary metabolites between lymphoid leukaemia and immune cells. In ALL, the causal relationship between 1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6) and ALL was mediated by CD62L-plasmacytoid DC%DC (mediated proportion=-2.84%, P=0.020). In CLL, the causal relationship between N6,n6,n6-trimethyllysine and CLL was mediated by HLA DR+ CD8br AC (mediated proportion=4.07%, P=0.021). Conclusion：This MR study provides evidence supporting specific causal relationships between the gut microbiota and lymphoid leukaemia, as well as between certain immune cells and lymphoid leukaemia with potential intermediary metabolites.

    Keywords: Gut Microbiota, immune cells, Lymphocytic leukemia, Mendelian Randomization Analysis, Serum metabolites

    Received: 24 May 2024; Accepted: 23 Aug 2024.

    Copyright: © 2024 Zhuang, Yang, Man, Wang and Shi. 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:
    Rong Yang, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
    Xiaoying Man, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
    Ruochen Wang, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
    Yifen Shi, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.