Gut microbiota, blood metabolites, & pan-cancer: a bidirectional Mendelian randomization & mediation analysis

被引:0
作者
Luan, Biqing [1 ]
Yang, Yang [2 ]
Yang, Qizhi [1 ]
Li, Zhiqiang [1 ]
Xu, Zhihui [1 ]
Chen, Yaqin [1 ]
Wang, Meiting [1 ]
Chen, Wenlin [2 ]
Ge, Fei [1 ]
机构
[1] Kunming Med Univ, Affiliated Hosp 1, Dept Breast Surg, Kunming 650032, Yunnan, Peoples R China
[2] Peking Univ, Kunming Med Univ,Canc Hosp Yunnan, Yunnan Canc Hosp,Affiliated Hosp 3, Yunnan Key Lab Breast Canc Precis Med,Dept breast, Kunming, Yunnan, Peoples R China
来源
AMB EXPRESS | 2025年 / 15卷 / 01期
基金
中国国家自然科学基金;
关键词
Gut microbiota; Pan-cancer; Blood metabolites; Mendelian randomization; Mediation analysis; Metabolic pathway enrichment analysis; SUSCEPTIBILITY LOCI; LUNG-CANCER; ASSOCIATION; INSTRUMENTS; BIAS;
D O I
10.1186/s13568-025-01866-w
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We propose using Mendelian randomization analysis on GWAS data and MetaboAnalyst to model gut microbiota, metabolic pathways, blood metabolites, and cancer risk. We examined 473 gut microbiota, 205 pathways, 1400 metabolites, and 8 cancers. Results were validated through bidirectional two-sample Mendelian Randomization (MR), heterogeneity tests, and pathway enrichment, leading to a mediation pathway model. We identified 129 gut microbiota, 57 pathways, and 463 metabolites linked to cancer, and 34 significant plasma pathways. 15 microbiota, 8 pathways, and 58 metabolites implicated in multiple cancers. Eight plasma metabolic pathways are involved in the development of multiple types of cancer. Through Multivariate Mendelian Randomization (MVMR) and mediation analysis, we found 9 mediation pathways, offering novel targets and research directions for cancer pathogenesis and treatment.
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页数:17
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共 66 条
  • [21] Digging deeper through glucose metabolism and its regulators in cancer and metastasis
    Ghanavat, Majid
    Shahrouzian, Mehdi
    Zayeri, Zeinab Deris
    Banihashemi, Sara
    Kazemi, Seyedeh Maryam
    Saki, Najmaldin
    [J]. LIFE SCIENCES, 2021, 264
  • [22] Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis
    Gharahkhani, Puya
    Fitzgerald, Rebecca C.
    Vaughan, Thomas L.
    Palles, Claire
    Gockel, Ines
    Tomlinson, Ian
    Buas, Matthew F.
    May, Andrea
    Gerges, Christian
    Anders, Mario
    Becker, Jessica
    Kreuser, Nicole
    Noder, Tania
    Venerito, Marino
    Veits, Lothar
    Schmidt, Thomas
    Manner, Hendrik
    Schmidt, Claudia
    Hess, Timo
    Boehmer, Anne C.
    Izbicki, Jakob R.
    Hoelscher, Arnulf H.
    Lang, Hauke
    Lorenz, Dietmar
    Schumacher, Brigitte
    Hackelsberger, Andreas
    Mayershofer, Rupert
    Pech, Oliver
    Vashist, Yogesh
    Ott, Katja
    Vieth, Michael
    Weismueller, Josef
    Noethen, Markus M.
    Attwood, Stephen
    Barr, Hugh
    Chegwidden, Laura
    de Caestecker, John
    Harrison, Rebecca
    Love, Sharon B.
    MacDonald, David
    Moayyedi, Paul
    Prenen, Hans
    Watson, R. G. Peter
    Iyer, Prasad G.
    Anderson, Lesley A.
    Bernstein, Leslie
    Chow, Wong-Ho
    Hardie, Laura J.
    Lagergren, Jesper
    Liu, Geoffrey
    [J]. LANCET ONCOLOGY, 2016, 17 (10) : 1363 - 1373
  • [23] The microbiome, cancer, and cancer therapy
    Helmink, Beth A.
    Khan, M. A. Wadud
    Hermann, Amanda
    Gopalakrishnan, Vancheswaran
    Wargo, Jennifer A.
    [J]. NATURE MEDICINE, 2019, 25 (03) : 377 - 388
  • [24] The MR-Base platform supports systematic causal inference across the human phenome
    Hemani, Gibran
    Zhengn, Jie
    Elsworth, Benjamin
    Wade, Kaitlin H.
    Haberland, Valeriia
    Baird, Denis
    Laurin, Charles
    Burgess, Stephen
    Bowden, Jack
    Langdon, Ryan
    Tan, Vanessa Y.
    Yarmolinsky, James
    Shihab, Hashem A.
    Timpson, Nicholas J.
    Evans, David M.
    Relton, Caroline
    Martin, Richard M.
    Smith, George Davey
    Gaunt, Tom R.
    Haycock, Philip C.
    [J]. ELIFE, 2018, 7
  • [25] Hibberd AA, 2017, BMJ OPEN GASTROENTER, V4, DOI 10.1136/bmjgast-2017-000145
  • [26] Gut microbiome causal impacts on the prognosis of breast cancer: a Mendelian randomization study
    Hong, Weimin
    Huang, Guoxin
    Wang, Danhong
    Xu, Yadan
    Qiu, Jie
    Pei, Bin
    Qian, Da
    Meng, Xuli
    [J]. BMC GENOMICS, 2023, 24 (01)
  • [27] Discovery of common and rare genetic risk variants for colorectal cancer
    Huyghe, Jeroen R.
    Bien, Stephanie A.
    Harrison, Tabitha A.
    Kang, Hyun Min
    Chen, Sai
    Schmit, Stephanie L.
    Conti, David V.
    Qu, Conghui
    Jeon, Jihyoun
    Edlund, Christopher K.
    Greenside, Peyton
    Wainberg, Michael
    Schumacher, Fredrick R.
    Smith, Joshua D.
    Levine, David M.
    Nelson, Sarah C.
    Sinnott-Armstrong, Nasa A.
    Albanes, Demetrius
    Alonso, M. Henar
    Anderson, Kristin
    Arnau-Collell, Coral
    Arndt, Volker
    Bamia, Christina
    Banbury, Barbara L.
    Baron, John A.
    Berndt, Sonja I.
    Bezieau, Stephane
    Bishop, D. Timothy
    Boehm, Juergen
    Boeing, Heiner
    Brenner, Hermann
    Brezina, Stefanie
    Buch, Stephan
    Buchanan, Daniel D.
    Burnett-Hartman, Andrea
    Butterbach, Katja
    Caan, Bette J.
    Campbell, Peter T.
    Carlson, Christopher S.
    Castellvi-Bel, Sergi
    Chan, Andrew T.
    Chang-Claude, Jenny
    Chanock, Stephen J.
    Chirlaque, Maria-Dolores
    Cho, Sang Hee
    Connolly, Charles M.
    Cross, Amanda J.
    Cuk, Katarina
    Curtis, Keith R.
    de la Chapelle, Albert
    [J]. NATURE GENETICS, 2019, 51 (01) : 76 - +
  • [28] The relationship between circulating lipids and breast cancer risk: A Mendelian randomization study
    Johnson, Kelsey E.
    Siewert, Katherine M.
    Klarin, Derek
    Damrauer, Scott M.
    Program, Va Million Veteran
    Chang, Kyong-Mi
    Tsao, Philip S.
    Assimes, Themistocles L.
    Maxwell, Kara N.
    Voight, Benjamin F.
    [J]. PLOS MEDICINE, 2020, 17 (09)
  • [29] KEGG for integration and interpretation of large-scale molecular data sets
    Kanehisa, Minoru
    Goto, Susumu
    Sato, Yoko
    Furumichi, Miho
    Tanabe, Mao
    [J]. NUCLEIC ACIDS RESEARCH, 2012, 40 (D1) : D109 - D114
  • [30] A practical guide to methods controlling false discoveries in computational biology
    Korthauer, Keegan
    Kimes, Patrick K.
    Duvallet, Claire
    Reyes, Alejandro
    Subramanian, Ayshwarya
    Teng, Mingxiang
    Shukla, Chinmay
    Alm, Eric J.
    Hicks, Stephanie C.
    [J]. GENOME BIOLOGY, 2019, 20 (1)