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. 2024 Nov 19:14:1453202.
doi: 10.3389/fonc.2024.1453202. eCollection 2024.

Gut microbiome's causal role in head and neck cancer: findings from mendelian randomization

Meng Lian  1   2 , Minghong Sun  3 , Boxuan Han  1   2 , Ancha Baranova  4   5 , Hongbao Cao  4 , Fuquan Zhang  6   7
Affiliations

Gut microbiome's causal role in head and neck cancer: findings from mendelian randomization

Meng Lian et al. Front Oncol. .

Abstract

Introduction: The gut microbiome (GM) has been implicated in cancer pathogenesis and treatment, including head and neck cancers (HNC). However, the specific microbial compositions influencing HNC and the underlying mechanisms remain largely unknown.

Methods: This study utilized published genome-wide association studies (GWAS) summary data-based two-sample Mendelian randomization (MR) to uncover the GM compositions that exert significant causal effects on HNC. Functional annotation and enrichment analysis were conducted to better understand the significant genetic variables and their connection with HNC. The HNC dataset included 2,281 cases and 314,193 controls. The GM GWAS data of 211 gut taxa (35 families, 20 orders, 16 classes, 9 phyla, and 131 genera) were obtained from the MibioGen consortium, involving 18,340 participants.

Results: MR analysis revealed four GM compositions exerting causal effects on HNC. Specifically, family Peptococcaceae.id.2024 was significantly associated with a 35% reduced risk of HNC (OR=0.65; 95%CI=0.48-0.90; P=0.0080). In contrast, genus DefluviitaleaceaeUCG-011.id.11287 (OR=1.54; 95%CI=1.13-2.09; P=0.0060), genus Gordonibacter.id.821 (OR=1.23; 95%CI=1.05-1.45; P=0.012), and genus Methanobrevibacter.id.123 (OR=1.28; 95%CI=1.01-1.62; P=0.040) showed a significant association with an increased risk of HNC. These GMs interact with genes and genetic variants involved in signaling pathways, such as GTPase regulation, influencing tumor progression and disease prognosis.

Conclusions: Our study demonstrates, for the first time, the causal influence of specific gut microbiome compositions on HNC, offering significant insights for advancing clinical research and personalized treatments. The identified GMs may serve as potential biomarkers or therapeutic targets, paving the way for innovative approaches in HNC diagnosis, prevention, and therapy.

Keywords: Mendelian randomization; enrichment analysis; functional annotation; gut microbiome; head and neck cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall workflow diagram of the study.
Figure 2
Figure 2
Causal effect of four gut microbiomes on head and neck cancers. (A) Effect of family.Peptococcaceae.id.2024; (B) effect of genus.DefluviitaleaceaeUCG011.id.11287; (C) Effect of genus.Gordonibacter.id.821; (D) Effect of genus.Methanobrevibacter.id.123. In each plot, the lines were the effect sizes (B) of the MR analysis. IVW, inverse variance weighted; WM, weighted median.
Figure 3
Figure 3
Forest plot of the casual effects of the four GMs on HNC.
Figure 4
Figure 4
Leave-One-Out plots illustrating the robustness of the MR analysis for four gut microbiota taxa. (A) family.Peptococcaceae.id.2024 on head and neck cancers; (B) genus.DefluviitaleaceaeUCG011.id.11287 on head and neck cancers; (C) genus.Gordonibacter.id.821 on head and neck cancers; (D) genus.Methanobrevibacter.id.123 on head and neck cancers.
Figure 5
Figure 5
Functional pathway connecting HNC and four GMs.
Figure 6
Figure 6
Ring diagram showing the causal association between four gut microbiota and head and neck cancer: Family Peptococcaceae (reduced risk); Genus Defluviitaleaceae UCG-011 (increased risk); Genus Gordonibacter (increased risk); Genus Methanobrevibacter (increased risk).
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