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. 2025 Jul-Aug;91(4):101634.
doi: 10.1016/j.bjorl.2025.101634. Epub 2025 Apr 30.

Causal relationship between gut microbiota and laryngeal cancer: a mendelian randomization analysis

Kaiyan Yi  1 , Yu Huang  1 , Yun Jiang  1 , Lingling Zhou  2
Affiliations

Causal relationship between gut microbiota and laryngeal cancer: a mendelian randomization analysis

Kaiyan Yi et al. Braz J Otorhinolaryngol. 2025 Jul-Aug.

Abstract

Objective: Laryngeal cancer incidence is rising globally; the role of gut microbiota remains underexplored. This study aimed to establish a causal link between gut microbiota and laryngeal cancer to inform preventive and therapeutic strategies.

Methods: Gut microbiota data from GWAS conducted by the MiBioGen consortium served as the exposure variable, with laryngeal cancer as the outcome variable. the exposure variable and the outcome variable were analyzed using Mendelian Randomization. The primary method was Inverse Variance Weighted analysis, with heterogeneity and pleiotropy assessed through Cochran's Q test, MR-Egger regression, and MR-PRESSO.

Results: In the study, we identified five bacterial taxa with potential causal relationships with laryngeal cancer risk: Higher levels of Clostridiaceae1 (OR = 0.9993, 95% CI 0.9986-0.9999, p = 0.0463) and Turicibacter (OR = 0.9995, 95% CI 0.9989-0.9999, p = 0.0384) were linked to reduced cancer risk, while Mollicutes RF9 (OR = 1.0010, 95% CI 1.0003-1.0016, p = 0.0027), Euryarchaeota (OR = 1.0004, 95% CI 1.0001-1.0007, p = 0.0234), and Cyanobacteria (OR = 1.0005, 95% CI 1.0000-1.0009, p = 0.0464) were associated with increased risk.

Conclusion: Our findings suggest a causal relationship between gut microbiota composition and laryngeal cancer risk. Clostridiaceae1 and Turicibacter may play a protective role, while Mollicutes RF9, Euryarchaeota, and Cyanobacteria could contribute to increased cancer susceptibility. These insights highlight potential microbiome-based strategies for early detection, prevention, and therapeutic intervention in laryngeal cancer.

Level of evidence: Level 5.

Keywords: GWAS; Gut microbiota; Laryngeal cancer; Mendelian randomization; The causal association.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flow chart of this study.
Fig. 2
Fig. 2
Scatter plots for causal SNPs effect of gut microbiota on laryngeal cancer. Each black point representing each SNP on the exposure (horizontal-axis) and on the outcome (vertical-axis) is plotted with error bars corresponding to each Standard Error (SE). (A) Euryarchaeota; (B) Cyanobacteria; (C) MollicutesRF9; (D) Clostridiaceae1; (E) Clostridiaceae1.
Fig. 3
Fig. 3
Forest plots of Leave-one-out analyses for causal SNP effect of gut microbiota on laryngeal cancer. The error bars indicate the 95% Confidence Interval (95% CI). (A) Euryarchaeota; (B) Cyanobacteria; (C) MollicutesRF9; (D) Clostridiaceae1; (E) Clostridiaceae1.
See this image and copyright information in PMC

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