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. 2025 Jul 15;15(1):106.
doi: 10.1186/s13568-025-01909-2.

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

Qicong Chen #  1 , Gang Wang #  1 , Jingcheng Shu #  2 , Xiaosu Zou  1 , Weiwei Miao  1 , Wenqian Nong  1 , Min Li  2 , Guiping Lan  2 , Wenlin Huang  2 , Xueying Huang  2 , Honglin Luo  3 , Shenhong Qu  4   5
Affiliations

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

Qicong Chen et al. AMB Express. .

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).

Keywords: Gut microbiome; Immune cells; Malignant neoplasm of nasopharynx; Mediation analysis; Mendelian randomization.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the ethics committee of The People's Hospital of Guangxi Zhuang Autonomous Region (KY-KJT-2023-101). This MR study only used the summary data of GWAS study, without any identifiable private information. Consent for publication: The authors declare consent for publication. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the study design and analysis strategy. a Overview of study design. Gut microbiota compositions and immune cell traits were regarded as the exposures in this MR study. b Strategy of MR analysis. Complete strategy of MR analysis includes IV filtration, MR analysis, sensitivity analyses, outlier detection and result visualization. c Strategy of mediation MR analysis. Step 1, assessment of the causal effects of gut microbiota on immune cell traits; step 2, estimation the causal effects of the selected immune cell traits on the risk of malignant neoplasms of nasopharynx
Fig. 2
Fig. 2
Results of MR analysis of gut microbiota compositions on the risk of malignant neoplasms of nasopharynx
Fig. 3
Fig. 3
Results of MR analysis of immune cell traits on the risk of malignant neoplasms of nasopharynx
Fig. 4
Fig. 4
Results of MR analysis of gut microbiota compositions on immune cell traits
Fig. 5
Fig. 5
Results of MVMR analysis and mediation MR analysis on the risk of malignant neoplasms of nasopharynx. a MVMR analysis of the effects of gut microbiota compositions and immune cell traits on the risk of malignant neoplasms of nasopharynx. b Mediation MR analysis of immune cell traits on the risk of malignant neoplasms of nasopharynx. E: exposure; M: mediators
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