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Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies. MATERIALS AND METHODS:...

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Autores principales: Chen, Zhitao, Shi, Weiguang, Chen, Kailei, Lu, Chicheng, Li, Xinyuan, Li, Qiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682188/
https://www.ncbi.nlm.nih.gov/pubmed/38033576
http://dx.doi.org/10.3389/fmicb.2023.1288525
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author Chen, Zhitao
Shi, Weiguang
Chen, Kailei
Lu, Chicheng
Li, Xinyuan
Li, Qiyong
author_facet Chen, Zhitao
Shi, Weiguang
Chen, Kailei
Lu, Chicheng
Li, Xinyuan
Li, Qiyong
author_sort Chen, Zhitao
collection PubMed
description BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies. MATERIALS AND METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms. RESULTS: Genetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment. CONCLUSION: Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.
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spelling pubmed-106821882023-11-30 Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis Chen, Zhitao Shi, Weiguang Chen, Kailei Lu, Chicheng Li, Xinyuan Li, Qiyong Front Microbiol Microbiology BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies. MATERIALS AND METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms. RESULTS: Genetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment. CONCLUSION: Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk. Frontiers Media S.A. 2023-11-14 /pmc/articles/PMC10682188/ /pubmed/38033576 http://dx.doi.org/10.3389/fmicb.2023.1288525 Text en Copyright © 2023 Chen, Shi, Chen, Lu, Li and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Chen, Zhitao
Shi, Weiguang
Chen, Kailei
Lu, Chicheng
Li, Xinyuan
Li, Qiyong
Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis
title Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis
title_full Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis
title_fullStr Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis
title_full_unstemmed Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis
title_short Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis
title_sort elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through mendelian randomization analysis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682188/
https://www.ncbi.nlm.nih.gov/pubmed/38033576
http://dx.doi.org/10.3389/fmicb.2023.1288525
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