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. 2024 May 30:14:1389678.
doi: 10.3389/fonc.2024.1389678. eCollection 2024.

Gut microbiota and oral cavity cancer: a two-sample bidirectional Mendelian randomization study

Zhijuan Sun  1 , Chunying Bai  2 , Dandan Hao  2 , Xiling Jiang  3 , Jianxing Chen  1   4
Affiliations

Gut microbiota and oral cavity cancer: a two-sample bidirectional Mendelian randomization study

Zhijuan Sun et al. Front Oncol. .

Abstract

This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC).

Objective: To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis.

Methods: Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MR-Egger intercept test.

Results: Our findings indicate, at the order level, Bacteroidales (OR = 0.9990, 95% CI = 0.9980-1.0000, P = 0.046), Burkholderiales (OR = 1.0009, 95% CI = 1.0001-1.0018, P = 0.033), and Victivallales (OR = 0.9979, 95% CI = 0.9962-0.9995, P = 0.037) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, Alcaligenaceae (OR = 1.0012, 95% CI = 1.0004-1.0019, P = 0.002) and Clostridiaceae1 (OR = 0.9970, 95% CI = 0.9948-0.9992, P = 0.027) show causality on OCC in IVW and MR-Egger analyses. At the genus level, Clostridiumsensustricto1 (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, P = 0.001; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, P = 0.035), Desulfovibrio (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, P = 0.016), Eggerthella (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, P = 0.048), Eubacterium fissicatena group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, P = 0.032), and Holdemanella (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, P = 0.018) are implicated in causing OCC in related analyses.

Conclusion: Our study identifies Burkholderiales order, Alcaligenaceae family, Desulfovibrio genus, and Eubacterium fissicatena group as causally increasing OCC risk. In contrast, Bacteroidales order, Victivallales order, Clostridiaceae1 family, Clostridiumsensustricto1 genus, Eggerthella genus, and Holdemanella genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology.

Keywords: GWAS; Mendelian randomization; causality; gut microbiota; oral cavity 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
Three key assumptions for a valid Mendelian randomization study.
Figure 2
Figure 2
The flowchart of the MR study revealing the causal relationship between gut microbiota and OCC.
Figure 3
Figure 3
Significant MR estimates of phylum-level gut microbiota (Lentisphaerae) on OCC. (A) forest plot; (B) leave-one-out analysis; (C) scatter plot; (D) funnel plot.
Figure 4
Figure 4
Significant MR estimates of class-level gut microbiota (Lentisphaeria) on OCC. (A) forest plot; (B) leave-one-out analysis; (C) scatter plot; (D) funnel plot.
Figure 5
Figure 5
Significant MR estimates of order-level gut microbiota (A) Bacteroidales (B) Burkholderiales (C) Victivallales on OCC. From top to bottom: forest plot; leave-one-out analysis; scatter plot; funnel plot.
Figure 6
Figure 6
Significant MR estimates of family-level gut microbiota (A) Alcaligenaceae (B) Clostridiaceae1 on OCC. From top to bottom: forest plot; leave-one-out analysis; scatter plot; funnel plot.
Figure 7
Figure 7
Significant MR estimates of genus-level gut microbiota (A) Clostridiumsensustricto1 (B) Desulfovibrio (C) Eggerthella (D) Eubacterium fissicatena group (E) Holdemanella on OCC. From top to bottom: forest plot; leave-one-out analysis; scatter plot; funnel plot.
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