胃微生物在胃癌进展中的作用

doi:10.3969/j.issn.1006-7795.2025.04.015

摘要/Abstract

摘要： 胃癌是一种临床常见肿瘤，其发病率和病死率均居恶性肿瘤前列。幽门螺杆菌（Helicobacter pylori, Hp）是胃癌的重要致癌因素，除Hp外胃内的其他微生物也在胃癌进展中扮演关键角色。胃微生物群的构成和多样性在不同胃病状态下显著不同，这可能影响胃癌的进展。Hp可通过多种毒力因子诱导胃上皮炎症和氧化应激，进而促进胃癌发生；非Hp微生物则可通过代谢变化和免疫调节等途径参与胃癌进程。近年来，随着高通量测序技术的发展，胃微生物的复杂性也逐渐被揭示，这为胃癌的早期预警和干预提供了新思路。因此，本文将全面综述胃微生物在胃癌进展中的作用。

关键词: 胃癌, 肿瘤, 微生物, 幽门螺杆菌, 机制, 测序

Abstract: Gastric cancer is a common clinical tumor, and its incidence and mortality rates rank among the top of malignant tumors. Helicobacter pylori (Hp) is an important carcinogenic factor for gastric cancer. Studies have found that in addition to Hp, other microorganisms in the stomach also play a key role in the progression of gastric cancer. The composition and diversity of the gastric microbiota vary significantly under different gastric disease conditions, which may affect the progression of gastric cancer. Hp can induce gastric epithelial inflammation and oxidative stress through various virulence factors, thereby promoting the occurrence of gastric cancer. Non-Hp microorganisms can be involved in the process of gastric cancer through pathways such as metabolic changes and immune regulation. In recent years, with the development of high-throughput sequencing technology, the complexity of gastric microbiota has gradually been revealed, which provides new insights for the early warning and intervention of gastric cancer. This article comprehensively review the role of gastric microbiota in the progression of gastric cancer.

Key words: gastric cancer, tumor, microbiome, Helicobacter pylori, mechanism, sequencing

中图分类号:

R573

刘思凡, 杨舒悦, 冀旭, 张政, 李鹏. 胃微生物在胃癌进展中的作用[J]. 首都医科大学学报, 2025, 46(4): 682-687.

Liu Sifan, Yang Shuyue, Ji Xu, Zhang Zheng, Li Peng. Research on the role of gastric microbiome in the progression of gastric cancer[J]. Journal of Capital Medical University, 2025, 46(4): 682-687.

参考文献

［1］Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin, 2024, 74(3):229-263.
［2］Smyth E C, Nilsson M, Grabsch H I, et al. Gastric cancer［J］. Lancet, 2020, 396(10251): 635-648.
［3］Sitarz R, Skierucha M, Mielko J, et al. Gastric cancer: epidemiology, prevention, classification, and treatment［J］. Cancer Manag Res, 2018, 10: 239-248.
［4］Liao W H, Wang J, Li Y C. Natural products based on Correa's cascade for the treatment of gastric cancer trilogy: current status and future perspective［J］. J Pharm Anal, 2025, 15(2): 101075.
［5］Peng R, Liu S, You W H, et al. Gastric microbiome alterations are associated with decreased CD8+tissue-resident memory T cells in the tumor microenvironment of gastric cancer［J］. Cancer Immunol Res, 2022, 10(10): 1224-1240.
［6］Wu M J, Tian C J, Zou Z W, et al. Gastrointestinal microbiota in gastric cancer: potential mechanisms and clinical applications-a literature review［J］. Cancers, 2024, 16(20): 3547.
［7］Moss S F, Shah S C, Tan M C, et al. Evolving concepts in Helicobacter pylori management［J］. Gastroenterology, 2024, 166(2): 267-283.
［8］Pan K F, Li W Q, Zhang L, et al. Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial［J］. Nat Med, 2024, 30(11): 3250-3260.
［9］Salvatori S, Marafini I, Laudisi F, et al. Helicobacter pylori and gastric cancer: pathogenetic mechanisms［J］. Int J Mol Sci, 2023, 24(3): 2895.
［10］Majewski M, Mertowska P, Mertowski S, et al. Microbiota and the immune system-actors in the gastric cancer story［J］. Cancers, 2022, 14(15): 3832.
［11］Ferreira R M, Pereira-Marques J, Pinto-Ribeiro I, et al. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota［J］. Gut, 2018, 67(2): 226-236.
［12］Coker O O, Dai Z W, Nie Y Z, et al. Mucosal microbiome dysbiosis in gastric carcinogenesis［J］. Gut, 2018, 67(6): 1024-1032.
［13］Chen X H, Wang A, Chu A N, et al. Mucosa-associated microbiota in gastric cancer tissues compared with non-cancer tissues［J］. Front Microbiol, 2019, 10: 1261.
［14］Gantuya B, El-Serag H B, Matsumoto T, et al. Gastric microbiota in helicobacter pylori-negative and -positive gastritis among high incidence of gastric cancer area［J］. Cancers, 2019, 11(4): 504.
［15］Tran S C, Bryant K N, Cover T L. The Helicobacter pylori cag pathogenicity island as a determinant of gastric cancer risk［J］. Gut Microbes, 2024, 16(1): 2314201.
［16］Chen B N, Liu X L, Yu P Y, et al. H.pylori-induced NF-κB-PIEZO1-YAP1-CTGF axis drives gastric cancer progression and cancer-associated fibroblast-mediated tumour microenvironment remodelling［J］. Clin Transl Med, 2023, 13(11): e1481.
［17］Schmidinger B, Petri K, Lettl C, et al. Helicobacter pylori binds human annexins via lipopolysaccharide to interfere with toll-like receptor 4 signaling［J］. PLoS Pathog, 2022, 18(2): e1010326.
［18］Suzuki M, Mimuro H, Kiga K, et al. Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation［J］. Cell Host Microbe, 2009, 5(1): 23-34.
［19］Che Y, Geng B, Xu Y, et al. Helicobacter pylori-induced exosomal Met educates tumour-associated macrophages to promote gastric cancer progression［J］. J Cell Mol Med, 2018, 22(11): 5708-5719.
［20］Baj J, Forma A, Sitarz M, et al. Helicobacter pylori virulence factors-mechanisms of bacterial pathogenicity in the gastric microenvironment［J］. Cells, 2020, 10(1): 27.
［21］Chmiela M, Kupcinskas J. Review: pathogenesis of Helicobacter pylori infection［J］. Helicobacter, 2019, 24(S1): e12638.
［22］Ito N, Tsujimoto H, Ueno H, et al. Helicobacter pylori-mediated immunity and signaling transduction in gastric cancer［J］. J Clin Med, 2020, 9(11): 3699.
［23］Li N, Xu H B, Ou Y R, et al. LPS-induced CXCR7 expression promotes gastric cancer proliferation and migration via the TLR4/MD-2 pathway［J］. Diagn Pathol, 2019, 14(1): 3.
［24］Luo Y H, Yan J, Mao Y F. Helicobacter pylori lipopolysaccharide: biological activities in vitro and in vivo, pathological correlation to human chronic gastritis and peptic ulcer［J］. World J Gastroenterol, 2004, 10(14): 2055-2059.
［25］Han L, Shu X, Wang J. Helicobacter pylori-mediated oxidative stress and gastric diseases: a review［J］. Front Microbiol, 2022, 13: 811258.
［26］Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond［J］. Nat Rev Mol Cell Biol, 2012, 13(2): 89-102.
［27］Baird M, Woon Ang P, Clark I, et al. The unfolded protein response is activated in Helicobacter-induced gastric carcinogenesis in a non-cell autonomous manner［J］. Lab Invest, 2013, 93(1): 112-122.
［28］Azad M B, Chen Y Q, Gibson S B. Regulation of autophagy by reactive oxygen species(ROS): implications for cancer progression and treatment［J］. Antioxid Redox Signal, 2009, 11(4): 777-790.
［29］Sakaguchi A A, Miura S, Takeuchi T, et al. Increased expression of inducible nitric oxide synthase and peroxynitrite in Helicobacter pylori gastric ulcer［J］. Free Radic Biol Med, 1999, 27(7/8): 781-789.
［30］Cherdantseva L A, Potapova O V, Sharkova T V, et al. Association of Helicobacter pylori and iNOS production by macrophages and lymphocytes in the gastric mucosa in chronic gastritis［J］. J Immunol Res, 2014, 2014: 762514.
［31］Wang F, Meng W B, Wang B Y, et al. Helicobacter pylori-induced gastric inflammation and gastric cancer. ［J］. Cancer Lett, 2014, 345(2): 196-202.
［32］Yamashita S, Nanjo S, Rehnberg E, et al. Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori［J］. Clin Epigenetics, 2019, 11(1): 191.
［33］Liu B, Bukhari I, Li F Z, et al. Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-catenin nuclear translocation［J］. J Adv Res, 2025, 69: 299-312.
［34］Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells［J］. Science, 2004, 306(5701): 1568-1571.
［35］Varon C, Dubus P, Mazurier F, et al. Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice［J］. Gastroenterology, 2012, 142(2): 281-291.
［36］Shao L L, Chen Z, Soutto M, et al. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer［J］. FASEB J, 2019, 33(1): 264-274.
［37］Ajani J A, Lee J, Sano T, et al. Gastric adenocarcinoma. ［J］. Nat Rev Dis Primers, 2017, 3: 17036.
［38］Yang T T, Cao N, Zhang H H, et al. Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications［J］. Helicobacter, 2018, 23(3): e12486.
［39］Zhang D, Tang Z Y, Huang H, et al. Metabolic regulation of gene expression by histone lactylation［J］. Nature, 2019, 574(7779): 575-580.
［40］Dawson M A, Kouzarides T. Cancer epigenetics: from mechanism to therapy［J］. Cell, 2012, 150(1): 12-27.
［41］Castaño-Rodríguez N, Goh K L, Fock K M, et al. Dysbiosis of the microbiome in gastric carcinogenesis［J］. Sci Rep, 2017, 7(1): 15957.
［42］Dicksved J, Lindberg M, Rosenquist M, et al. Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls. ［J］. J Med Microbiol, 2009, 58(Pt 4): 509-516.
［43］Chan A W, Gill R S, Schiller D, et al. Potential role of metabolomics in diagnosis and surveillance of gastric cancer［J］. World J Gastroenterol, 2014, 20(36): 12874-12882.
［44］Yuan L, Pan L B, Wang Y Z, et al. Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression［J］. Cell Discov, 2024, 10(1): 117.
［45］Zeng R, Sung J J Y, Yu J. New pathogen for gastric cancer: Streptococcus anginosus［J］. Clin Transl Med, 2024, 14(12): e70104.
［46］Wang Z S, Mou R S, Jin S Y, et al. Streptococcus anginosus promotes gastric cancer progression via GSDME-mediated pyroptosis pathway: molecular mechanisms of action of GSDME, cleaved caspase-3, and NLRP3 proteins［J］. Int J Biol Macromol, 2025, 307(Pt 4): 142341.
［47］Barra W F, Sarquis D P, Khayat A S, et al. Gastric cancer microbiome［J］. Pathobiology, 2021, 88(2): 156-169.
［48］Wen F P, Han Y, Zhang H, et al. Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression［J］. Nat Commun, 2024, 15(1): 10543.
［49］Zhou Y Q, Jiang J X, He S, et al. Epstein-Barr virus hijacks histone demethylase machinery to drive epithelial malignancy progression through KDM5B upregulation［J］. Signal Transduct Target Ther, 2025, 10(1): 83.
［50］Liu J, Wang H Y, Zhang S, et al. Identification of shared and disease-specific intratumoral microbiome-host gene associations in gastrointestinal tumors［J］. Physiol Genomics, 2024, 56(11): 699-710.
［51］Wang G J, Wang H J, Ji X, et al. Intratumoral microbiome is associated with gastric cancer prognosis and therapy efficacy［J］. Gut Microbes, 2024, 16(1): 2369336.
［52］Abate M, Vos E, Gonen M, et al. A novel microbiome signature in gastric cancer: a two independent cohort retrospective analysis［J］. Ann Surg, 2022, 276(4): 605-615.
［53］Gao W, Li F F, Wu T, et al. Prognostic stratification of gastric cancer patients by intratumoral microbiota-mediated tumor immune microenvironment［J］. Microb Pathog, 2025, 200: 107296.
［54］Yue K L, Sheng D S, Xue X X, et al. Bidirectional mediation effects between intratumoral microbiome and host DNA methylation changes contribute to stomach adenocarcinoma［J］. Microbiol Spectr, 2023, 11(4): e0090423.
［55］Shin W S, Xie F D, Chen B N, et al. Exploring the microbiome in gastric cancer: assessing potential implications and contextualizing microorganisms beyond H. pylori and Epstein-Barr virus［J］. Cancers, 2023, 15(20): 4993.
［56］Toyoshima O, Nishizawa T, Koike K. Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis［J］. World J Gastroenterol, 2020, 26(5): 466-477.
［57］Peng X, Yao S Q, Huang J, et al. Alterations in bacterial community dynamics from noncancerous to gastric cancer［J］. Front Microbiol, 2023, 14: 1138928.

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