孟德尔随机化研究口腔菌群和循环代谢物在胆道恶性肿瘤中的作用

doi:10.3969/j.issn.1006-5725.2025.24.021

Abstract

Abstract:

Objective To systematically evaluate the causal relationships between oral microbiota， circulating metabolites， and biliary tract cancer （BTC） using Mendelian randomization （MR） and mediation analysis， and to elucidate the mediatory role of metabolites. Methods Using two-sample bidirectional Mendelian randomization and mediation analysis， we analyzed data from the China National GeneBank Life Data Platform and the BioBank Japan. Primary causal inference was based on inverse variance weighting （IVW）， supplemented by Bayesian weighted MR， linkage disequilibrium score regression， reverse MR， and sensitivity analyses. Results Thirteen salivary microbial taxa （e.g.， Prevotella seregens mgs 811， P = 0.013， OR = 2.387） and nineteen tongue dorsum microbial taxa （e.g.， Eikenella corrodens mgs 3538， P = 0.015， OR = 2.635） demonstrated significant associations with BTC risk. Concurrently， direct bilirubin （OR = 1.768） and lead （OR = 2.448） were identified as risk factors， whereas manganese （OR = 0.509） and citrulline （OR = 0.440） were protective factors. Mediation analysis revealed that three blood metabolites indirectly mediated the effects of five bacterial taxa on BTC， with a maximum mediation proportion reaching 10.3%. Conclusion This study demonstrates causal associations among oral microbiota， circulating metabolites， and BTC， thereby providing a theoretical foundation for precision prevention and treatment strategies rooted in the microbiota-metabolite axis.

Key words: biliary tract cancer, oral microbiota, circulating metabolites, Mendelian randomization

CLC Number:

Qiaobin HU,Zhida DAI,Zhixiang ZHANG,Ziyin GUO,Yiyi LIU,Chunlei ZHANG,Jinghua. LI. Mendelian randomization analysis reveals causal associations of oral microbiome and circulating metabolites with biliary tract cancer[J]. The Journal of Practical Medicine, 2025, 41(24): 3958-3968.

Figures/Tables 10

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References 44

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部位	微生物名称	遗传相关性	标准误差	P值
唾液	Campylobacter A concisus I mgs 556	0.147	0.519	0.777
	Lachnoanaerobaculum sp000296385 mgs 2787	-0.690	0.656	0.293
	Lancefieldella sp000564995 mgs 1829	0.048	0.387	0.901
	Prevotella melaninogenica mgs 1984	0.702	0.720	0.329
	Prevotella multiformis mgs 380	0.080	0.225	0.723
	Streptococcus mitis AT mgs 1319	-0.124	0.440	0.778
	Streptococcus mitis L mgs 538	0.465	0.621	0.454
舌背	Aggregatibacter segnis mgs 1370	0.079	0.550	0.886
	Aggregatibacter sp000466335 mgs 2199	0.073	0.622	0.907
	Alloprevotella rava mgs 541	-0.075	0.328	0.818
	Haemophilus haemolyticus mgs 2719	-0.473	0.686	0.490
	Lachnoanaerobaculum sp000287675 mgs 3128	-0.320	0.892	0.720
	Pauljensenia cellulosilytica mgs 3249	-0.222	1.087	0.838
	Porphyromonas uenonis mgs 507	0.298	0.510	0.559
	Solobacterium moorei mgs 709	0.448	0.704	0.524
	Streptococcus mitis L mgs 538	0.609	0.724	0.401
	Streptococcus oralis Z mgs 3165	0.536	0.626	0.392
	SZUA-359	0.199	0.503	0.692

部位	微生物名称	代谢物	OR（95%CI）	P值	FDR q值
唾液	Lancefieldella sp000564995 mgs 1829	直接胆红素	0.874（0.772 ~ 0.990）	0.034	0.043
	Prevotella seregens mgs 811	直接胆红素	1.166（1.045 ~ 1.302）	0.006	0.032
	Streptococcus mitis L mgs 538	锰	0.899（0.813 ~ 0.993)）	0.037	0.043
舌背	Aggregatibacter segnis mgs 1370	直接胆红素	1.099（1.008 ~ 1.197）	0.031	0.043
	Eikenella corrodens mgs 3538	锰	0.899（0.826 ~ 0.978）	0.014	0.032
	Streptococcus oralis Z mgs 3165	瓜氨酸	1.083（1.017 ~ 1.154）	0.013	0.032

部位	微生物名称	代谢物	总效应	间接效应	中介效应
唾液	Lancefieldella sp000564995 mgs 1829	直接胆红素	-0.832	-0.077	0.093
	Prevotella seregens mgs 811	直接胆红素	0.870	0.088	0.102
舌背	Aggregatibacter segnis mgs 1370	直接胆红素	0.526	0.054	0.103
	Eikenella corrodens mgs 3538	锰	0.969	0.072	0.074
	Streptococcus oralis Z mgs 3165	瓜氨酸	-0.817	-0.072	0.088

Mendelian randomization analysis reveals causal associations of oral microbiome and circulating metabolites with biliary tract cancer

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