AUTHOR=Sun Zhijuan , Bai Chunying , Hao Dandan , Jiang Xiling , Chen Jianxing 

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

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1389678

DOI=10.3389/fonc.2024.1389678

ISSN=2234-943X

ABSTRACT=<p>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).</p><sec><title>Objective</title><p>To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>Our findings indicate, at the order level, <italic>Bacteroidales</italic> (OR = 0.9990, 95% CI = 0.9980–1.0000, <italic>P</italic> = <italic>0.046</italic>), <italic>Burkholderiales</italic> (OR = 1.0009, 95% CI = 1.0001–1.0018, <italic>P</italic> = <italic>0.033</italic>), and <italic>Victivallales</italic> (OR = 0.9979, 95% CI = 0.9962–0.9995, <italic>P</italic> = <italic>0.037</italic>) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, <italic>Alcaligenaceae</italic> (OR = 1.0012, 95% CI = 1.0004–1.0019, <italic>P</italic> = <italic>0.002</italic>) and <italic>Clostridiaceae1</italic> (OR = 0.9970, 95% CI = 0.9948–0.9992, <italic>P</italic> = <italic>0.027</italic>) show causality on OCC in IVW and MR-Egger analyses. At the genus level, <italic>Clostridiumsensustricto1</italic> (IVW, OR = 0.9987, 95% CI = 0.9980–0.9995, <italic>P</italic> = <italic>0.001</italic>; MR-Egger, OR = 0.9978, 95% CI = 0.9962–0.9995, <italic>P</italic> = <italic>0.035</italic>), <italic>Desulfovibrio</italic> (IVW, OR = 1.0008, 95% CI = 1.0001–1.0015, <italic>P</italic> = <italic>0.016</italic>), <italic>Eggerthella</italic> (IVW, OR = 0.9995, 95% CI = 0.9990–1.0000, <italic>P</italic> = <italic>0.048</italic>), <italic>Eubacterium fissicatena</italic> group (IVW, OR = 1.0005, 95% CI = 1.0000–1.0009, <italic>P</italic> = <italic>0.032</italic>), and <italic>Holdemanella</italic> (IVW, OR = 0.9994, 95% CI = 0.9989–0.9999, <italic>P</italic> = <italic>0.018</italic>) are implicated in causing OCC in related analyses.</p></sec><sec><title>Conclusion</title><p>Our study identifies <italic>Burkholderiales</italic> order, <italic>Alcaligenaceae</italic> family, <italic>Desulfovibrio</italic> genus, and <italic>Eubacterium fissicatena</italic> group as causally increasing OCC risk. In contrast, <italic>Bacteroidales</italic> order, <italic>Victivallales</italic> order, <italic>Clostridiaceae1</italic> family, <italic>Clostridiumsensustricto1</italic> genus, <italic>Eggerthella</italic> genus, and <italic>Holdemanella</italic> 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.</p></sec>