The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis

Abstract This study focused on the relationships among gut microbiota, plasma protein ratios, and tuberculosis. Given the unclear causal relationship between gut microbiota and tuberculosis and the scarcity of research on relevant plasma protein ratios in tuberculosis, Mendelian randomization analys...

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Main Authors: Hanxin Wu, Weijie Ma, Liangyu Zhu, Li Peng, Xun Huang, Lei Zhong, Rui Yang, Bingxue Li, Weijiang Ma, Li Gao, Xinya Wu, Jieqin Song, Suyi Luo, Fukai Bao, Aihua Liu
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87160-y
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author Hanxin Wu
Weijie Ma
Liangyu Zhu
Li Peng
Xun Huang
Lei Zhong
Rui Yang
Bingxue Li
Weijiang Ma
Li Gao
Xinya Wu
Jieqin Song
Suyi Luo
Fukai Bao
Aihua Liu
author_facet Hanxin Wu
Weijie Ma
Liangyu Zhu
Li Peng
Xun Huang
Lei Zhong
Rui Yang
Bingxue Li
Weijiang Ma
Li Gao
Xinya Wu
Jieqin Song
Suyi Luo
Fukai Bao
Aihua Liu
author_sort Hanxin Wu
collection DOAJ
description Abstract This study focused on the relationships among gut microbiota, plasma protein ratios, and tuberculosis. Given the unclear causal relationship between gut microbiota and tuberculosis and the scarcity of research on relevant plasma protein ratios in tuberculosis, Mendelian randomization analysis (MR) was employed for in-depth exploration. By analyzing the GWAS data of individuals with European ancestry (the FinnGen dataset included 409,568 controls and 2613 cases), using the two-sample MR method, we focused on evaluating the impact of immunocyte-mediated gut microbiota on tuberculosis and the associations between 2821 plasma protein-to-protein ratios and tuberculosis. Particularly, the mediation effect was emphasized in the exploration. The results showed that 19 gut microbiotas were associated with tuberculosis. An7 indirectly affected tuberculosis through immunocyte (CD4 on CM CD4+), with a masking effect ratio of 0.008, demonstrating immune cells’ mediating role in the association between gut microbiota and tuberculosis. Meanwhile, the MR analysis revealed that 127 plasma protein-to-protein ratios were associated with tuberculosis. In conclusion, this study not only confirmed the impact of immunocyte-mediated gut microbiota on tuberculosis and clarified the mediating mechanism therein but also identified plasma protein-to-protein ratios related to tuberculosis, providing novel and valuable ideas for diagnosing and treating tuberculosis.
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spelling doaj-art-57491e171cb14ce4b4fda9d3f4f522682025-01-26T12:31:47ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87160-yThe association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysisHanxin Wu0Weijie Ma1Liangyu Zhu2Li Peng3Xun Huang4Lei Zhong5Rui Yang6Bingxue Li7Weijiang Ma8Li Gao9Xinya Wu10Jieqin Song11Suyi Luo12Fukai Bao13Aihua Liu14Yunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityYunnan Provincial Key Laboratory of Children’s Major Diseases Research, School of Basic Medicine, Kunming Medical UniversityAbstract This study focused on the relationships among gut microbiota, plasma protein ratios, and tuberculosis. Given the unclear causal relationship between gut microbiota and tuberculosis and the scarcity of research on relevant plasma protein ratios in tuberculosis, Mendelian randomization analysis (MR) was employed for in-depth exploration. By analyzing the GWAS data of individuals with European ancestry (the FinnGen dataset included 409,568 controls and 2613 cases), using the two-sample MR method, we focused on evaluating the impact of immunocyte-mediated gut microbiota on tuberculosis and the associations between 2821 plasma protein-to-protein ratios and tuberculosis. Particularly, the mediation effect was emphasized in the exploration. The results showed that 19 gut microbiotas were associated with tuberculosis. An7 indirectly affected tuberculosis through immunocyte (CD4 on CM CD4+), with a masking effect ratio of 0.008, demonstrating immune cells’ mediating role in the association between gut microbiota and tuberculosis. Meanwhile, the MR analysis revealed that 127 plasma protein-to-protein ratios were associated with tuberculosis. In conclusion, this study not only confirmed the impact of immunocyte-mediated gut microbiota on tuberculosis and clarified the mediating mechanism therein but also identified plasma protein-to-protein ratios related to tuberculosis, providing novel and valuable ideas for diagnosing and treating tuberculosis.https://doi.org/10.1038/s41598-025-87160-yMendelian randomization (MR)TuberculosisGut microbiotaImmunocyteProtein-to-protein ratios
spellingShingle Hanxin Wu
Weijie Ma
Liangyu Zhu
Li Peng
Xun Huang
Lei Zhong
Rui Yang
Bingxue Li
Weijiang Ma
Li Gao
Xinya Wu
Jieqin Song
Suyi Luo
Fukai Bao
Aihua Liu
The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis
Scientific Reports
Mendelian randomization (MR)
Tuberculosis
Gut microbiota
Immunocyte
Protein-to-protein ratios
title The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis
title_full The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis
title_fullStr The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis
title_full_unstemmed The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis
title_short The association of gut microbiota, immunocyte dynamics, and protein–protein ratios with tuberculosis susceptibility: a Mendelian randomization analysis
title_sort association of gut microbiota immunocyte dynamics and protein protein ratios with tuberculosis susceptibility a mendelian randomization analysis
topic Mendelian randomization (MR)
Tuberculosis
Gut microbiota
Immunocyte
Protein-to-protein ratios
url https://doi.org/10.1038/s41598-025-87160-y
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