Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx

Abstract Observational studies have suggested associations among the gut microbiome, immune cells, and the risk of malignant neoplasms of nasopharynx. However, the causality of these relationships remains unclear. Thus, we conducted multiple Mendelian Randomization analyses to estimate the causal as...

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Main Authors: Qicong Chen, Gang Wang, Jingcheng Shu, Xiaosu Zou, Weiwei Miao, Wenqian Nong, Min Li, Guiping Lan, Wenlin Huang, Xueying Huang, Honglin Luo, Shenhong Qu
Format: Article
Language:English
Published: SpringerOpen 2025-07-01
Series:AMB Express
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Online Access:https://doi.org/10.1186/s13568-025-01909-2
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author Qicong Chen
Gang Wang
Jingcheng Shu
Xiaosu Zou
Weiwei Miao
Wenqian Nong
Min Li
Guiping Lan
Wenlin Huang
Xueying Huang
Honglin Luo
Shenhong Qu
author_facet Qicong Chen
Gang Wang
Jingcheng Shu
Xiaosu Zou
Weiwei Miao
Wenqian Nong
Min Li
Guiping Lan
Wenlin Huang
Xueying Huang
Honglin Luo
Shenhong Qu
author_sort Qicong Chen
collection DOAJ
description Abstract Observational studies have suggested associations among the gut microbiome, immune cells, and the risk of malignant neoplasms of nasopharynx. However, the causality of these relationships remains unclear. Thus, we conducted multiple Mendelian Randomization analyses to estimate the causal association of gut microbiota with the risk of malignant neoplasms of nasopharynx and to evaluate the mediating effect of immune cells on this causal pathway. Genetic variants extracted from genome-wide association studies of human gut microbiota compositions (n = 211), immune cell traits (n = 731) and malignant neoplasms of nasopharynx served as instrumental variables for calculating causal associations and mediating effects. Four gut microbiota compositions and eight immune cell traits exhibited detrimental causal effects, while three gut microbiota compositions and fifteen immune cell traits demonstrated protective effects. Interestingly, the causal association of genus Candidatus Soleaferrea id.11350 was no longer significant after adjusting for two established immune cell traits (HLA DR +  + monocyte %leukocyte and HLA DR +  + monocyte % monocyte). Moreover, HLA DR +  + monocyte %leukocyte exhibited a mediating effect (OR 0.75, 95% CI 0.59–0.96) on the causal pathway of genus Candidatus Soleaferrea id.11350–malignant neoplasms of nasopharynx, with a mediating proportion of 21.59%. To our knowledge, this study is the first to identify potential therapeutic targets and elucidate mechanistic insights for malignant neoplasms of nasopharynx interventions involving gut microbiota and immune cell traits; however, these findings warrant further validation through adequately powered randomized clinical trials (RCTs). Graphical abstract
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spelling doaj-art-3f49c52286ca4df582d19316efd2322c2025-08-20T04:03:07ZengSpringerOpenAMB Express2191-08552025-07-0115111310.1186/s13568-025-01909-2Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynxQicong Chen0Gang Wang1Jingcheng Shu2Xiaosu Zou3Weiwei Miao4Wenqian Nong5Min Li6Guiping Lan7Wenlin Huang8Xueying Huang9Honglin Luo10Shenhong Qu11Research Center of Oncology, Guangxi Academy of Medical SciencesResearch Center of Oncology, Guangxi Academy of Medical SciencesDepartment of Otolaryngology and Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous RegionResearch Center of Oncology, Guangxi Academy of Medical SciencesResearch Center of Oncology, Guangxi Academy of Medical SciencesResearch Center of Oncology, Guangxi Academy of Medical SciencesDepartment of Otolaryngology and Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Otolaryngology and Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Otolaryngology and Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Otolaryngology and Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous RegionResearch Center of Oncology, Guangxi Academy of Medical SciencesResearch Center of Oncology, Guangxi Academy of Medical SciencesAbstract Observational studies have suggested associations among the gut microbiome, immune cells, and the risk of malignant neoplasms of nasopharynx. However, the causality of these relationships remains unclear. Thus, we conducted multiple Mendelian Randomization analyses to estimate the causal association of gut microbiota with the risk of malignant neoplasms of nasopharynx and to evaluate the mediating effect of immune cells on this causal pathway. Genetic variants extracted from genome-wide association studies of human gut microbiota compositions (n = 211), immune cell traits (n = 731) and malignant neoplasms of nasopharynx served as instrumental variables for calculating causal associations and mediating effects. Four gut microbiota compositions and eight immune cell traits exhibited detrimental causal effects, while three gut microbiota compositions and fifteen immune cell traits demonstrated protective effects. Interestingly, the causal association of genus Candidatus Soleaferrea id.11350 was no longer significant after adjusting for two established immune cell traits (HLA DR +  + monocyte %leukocyte and HLA DR +  + monocyte % monocyte). Moreover, HLA DR +  + monocyte %leukocyte exhibited a mediating effect (OR 0.75, 95% CI 0.59–0.96) on the causal pathway of genus Candidatus Soleaferrea id.11350–malignant neoplasms of nasopharynx, with a mediating proportion of 21.59%. To our knowledge, this study is the first to identify potential therapeutic targets and elucidate mechanistic insights for malignant neoplasms of nasopharynx interventions involving gut microbiota and immune cell traits; however, these findings warrant further validation through adequately powered randomized clinical trials (RCTs). Graphical abstracthttps://doi.org/10.1186/s13568-025-01909-2Malignant neoplasm of nasopharynxGut microbiomeImmune cellsMendelian randomizationMediation analysis
spellingShingle Qicong Chen
Gang Wang
Jingcheng Shu
Xiaosu Zou
Weiwei Miao
Wenqian Nong
Min Li
Guiping Lan
Wenlin Huang
Xueying Huang
Honglin Luo
Shenhong Qu
Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx
AMB Express
Malignant neoplasm of nasopharynx
Gut microbiome
Immune cells
Mendelian randomization
Mediation analysis
title Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx
title_full Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx
title_fullStr Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx
title_full_unstemmed Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx
title_short Mendelian randomization analysis of gut microbiota-immune cell interactions in malignant neoplasm of nasopharynx
title_sort mendelian randomization analysis of gut microbiota immune cell interactions in malignant neoplasm of nasopharynx
topic Malignant neoplasm of nasopharynx
Gut microbiome
Immune cells
Mendelian randomization
Mediation analysis
url https://doi.org/10.1186/s13568-025-01909-2
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