厦门大学学报（自然科学版）2026，Vol.65Issue(1)：56-67,12.DOI:10.6043/j.issn.0438-0479.202505015
肿瘤细菌的发现、作用机制及其药物转化进展
Advances in tumor bacteria:discovery,functional mechanisms,and therapeutic translation
摘要
Abstract
[Background]Microorganisms are widely present in diverse sites of the human body,where their intricate interactions with the host critically influence both human health and disease.Accumulating evidence indicates that various tumors,once considered sterile,harbor their own characteristic microbial consortia,collectively termed the"tumor microbiome".Bacteria constitute an important part of the tumor micro biome.These microorganisms are increasingly recognized not merely as passive bystanders but as active components of the complex tumor microenvironment(TME).Within the TME,these bacteria modulate multiple aspects of tumorigenesis'including tumor initiation,progression,metastasis,and therapeutic response.These foundational discoveries have paved the way for broader investigations into the complex roles of microbial communities in oncology.[Progress]Extensive research has unveiled tumor-type-specific bacterial signatures,highlighting the dualistic and complex roles of these tumor bacteria.Several bacterial species are now implicated in carcinogenesis.For instance,Helicobacter pylori is a well-established cause of gastric cancer,while Fusobacterium nucleatum is frequently linked to colorectal cancer(CRC)progression.Other examples include enterotoxigenic Bacteroides fragilis(ETBF)in CRC.Tumor bacteria promote oncogenesis through multiple mechanisms:1)Induction of genomic instability through bacterial genotoxins.The colibactin/cytolethal distending toxin from certain tumor bacteria can induce DNA injury and promote mutations essential for tumorigenesis.Additionally,tumor bacteria can induce epigenetic alterations,as some bacteria promote aberrant DNA methylation of genes in tumor cells,which in turn affects their progression and metastasis.2)Modulation of oncogenic signaling pathways.Virulence factors(CagA/FadA/BFT)produced by tumor bacteria can interact with host cells to influence critical signaling pathways,thus exerting an integrative impact on the physiological state of tumor cells.3)Promotion of immune evasion by creating an immunosuppressive TME.Some proteins(CagA/Fap2)from tumor bacteria can interact with immune cells,impairing their cytotoxic functions and allowing tumor cells to escape immune surveillance.4)Metabolism of chemo therapeutics.T umor bacteria can express enzymes like cytidine deaminase that metabolize drugs such as gemcitabine into inactive forms,thereby conferring therapeutic resistance.Conversely,certain bacteria demonstrate anti-tumor properties.Some bacteria can activate T cells that subsequently cross-react with a similar tumor antigen,leading to effective tumor cell clearance via immune reaction.The clinical applications of tumor bacteria also represent an emerging frontier.Distinct microbial signatures in tumors offer great potential as usable diagnostic and prognostic biomarkers,with specific bacterial profiles correlating with patient survival in various cancers.Therapeutic strategies are also emerging.These include using antibiotics to eliminate carcinogenic bacteria and developing engineered bacteria as drug delivery carriers.These bacteria can be engineered to selectively colonize tumors,delivering cytotoxic agents or converting pro-drugs into active therapeutic agents locally,thus enabling highly targeted cancer treatments.[Perspective]Despite this remarkable progress,the intricate and dynamic molecular interactions among tumor bacteria,host tumor cells,and the immune system remain to be fully elucidated.Furthermore,a framework for rigorously evaluating the safety and efficacy of interventions targeting tumor bacteria is critically needed to facilitate their clinical translation.Future research warrants attention in the following directions:1)developing and standardizing high-sensitivity microbial detection technologies capable of accurately profiling the low-biomass tumor bacteria;2)unraveling the spatiotemporal dynamics of tumor bacterial communities and functionally characterizing their metabolic products;3)establishing validated bacterial signatures as biomarkers for cancer diagnosis,patient risk stratification,and predicting therapeutic responses;and 4)designing personalized microbial-based therapeutic strategies for cancer treatment.Through a multi-disciplinary approach,the field of tumor microbiology holds significant potential to transform our understanding of cancer and to yield innovative breakthroughs in its diagnosis and treatment.关键词
肿瘤微生物组/肿瘤细菌/肿瘤免疫逃逸/细菌治疗Key words
tumor microbiome/tumor bacteria/tumor immune evasion/bacterial therapy分类
生物科学引用本文复制引用
黄逸群,邓贤明..肿瘤细菌的发现、作用机制及其药物转化进展[J].厦门大学学报（自然科学版）,2026,65(1):56-67,12.基金项目
国家自然科学基金(22025702) （22025702）
国家重点研发计划(2022YFC2804100) （2022YFC2804100）
厦门南方海洋中心项目(23YYZP020QCB26) （23YYZP020QCB26）
教育部与国家外国专家局"111计划"(BP2018017) （BP2018017）
国家资助博士后研究人员计划(GZC20251742) （GZC20251742）
