Evidence map›Paper›PMID 41466002›Full record

ArticleMedicine2025

Causal relationships among gut microbiota, plasma metabolites, and hepatocellular carcinoma: A mediation Mendelian randomization study.

Xiaoning Zeng, Sirou Li, Xiaoli Xiong, Ying Lu

Abstract read
In one paragraph

Article in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Xiaoning ZengDepartment of Clinical Laboratory Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.ORCID 0009-0002-1153-641
Sirou LiDepartment of Clinical Laboratory Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Xiaoli XiongDepartment of Radiology, Guizhou Branch of Shanghai Children's Medical Center Shanghai JiaoTong University School of Medicine, Guiyang City, Guizhou Province, China.
Ying LuDepartment of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Observational studies have revealed an association between gut microbiota and hepatocellular carcinoma (HCC), but the causal relationship is unclear. This study investigated the causal relationship between gut microbiota and HCC and quantified the potential mediating role of plasma metabolites using Mendelian randomization (MR) analysis. Two-sample MR analysis was performed to investigate the relationship between 211 gut microbiota species, 1400 plasma metabolites, and HCC using summary data from genome-wide association studies. Furthermore, a 2-step approach quantified the mediating effect of the gut microbiota on HCC through plasma metabolites. Effect estimates were primarily obtained using the inverse variance weighting method, and the robustness of the causal relationships was further assessed using Bayesian weighted MR. Our MR analysis revealed that the Coprococcus2 genus reduces the risk of HCC by increasing the plasma phosphate-to-ethylenediaminetetraacetic acid ratio (phosphate-to-EDTA ratio). Specifically, this ratio mediates 7.77% (95% CI: 2.20%-8.72%) of the causal relationship between Coprococcus2 and HCC. Conversely, the Ruminococcus2 genus significantly elevates the risk of HCC by lowering the plasma levels of 1-oleoyl-2-linoleoyl-glycero-3-phosphoethanolamine (1-oleoyl-2-linoleoyl-GPE) (18:1/18:2), with a mediating effect of 5.21% (95% CI: 0.94%-6.88%). No heterogeneity or pleiotropy was observed in any of the results, and both inverse variance weighting (IVW) and Bayesian weighted MR analyses confirmed the robustness of causal relationships. This study establishes a causal relationship between specific gut microbiota and HCC while also identifying the mediating role of plasma metabolites, which may influence the liver which may influence the development of liver cancer through bile metabolism or fat metabolism. These findings offer potential biomarkers and targeted strategies for early diagnosis and intervention of HCC.

Indexed as

Carcinoma, HepatocellularGastrointestinal MicrobiomeLiver NeoplasmsBayes TheoremGenome-Wide Association StudyHumansMendelian Randomization Analysiscausal relationshipgut microbiotahepatocellular carcinomamediator effectMendelian randomizationplasma metabolites

Identifiers

PMID41466002
PMCPMC12746965

What Socratic holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.