Metagenomic studies using next-generation sequencing technologies have revealed rich human intestinal microbiome, which likely influence host immunity and health conditions including cancer. Evidence indicates a biological link between altered microbiome and cancers in the digestive system. Escherichia coli and Bacteroides fragilis have been found to be enriched in colorectal mucosal tissues from patients with familial adenomatous polyposis that is caused by germline APC mutations. In addition, recent studies have found enrichment of certain oral bacteria, viruses, and fungi in tumor tissue and fecal specimens from patients with gastrointestinal cancer. An integrative approach is required to elucidate the role of microorganisms in the pathogenic process of gastrointestinal cancers, which develop through the accumulation of somatic genetic and epigenetic alterations in neoplastic cells, influenced by host genetic variations, immunity, microbiome, and environmental exposures. The transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to link germline genetics and environmental factors (including diet, lifestyle, and pharmacological factors) to pathologic phenotypes. The integration of microbiology into the MPE model (microbiology–MPE) can contribute to better understanding of the interactive role of environment, tumor cells, immune cells, and microbiome in various diseases. We review major clinical and experimental studies on the microbiome, and describe emerging evidence from the microbiology–MPE research in gastrointestinal cancers. Together with basic experimental research, this new research paradigm can help us to develop new prevention and treatment strategies for gastrointestinal cancers through targeting of the microbiome.

使用下一代测序技术的宏基因组研究揭示了丰富的人类肠道微生物组，这可能会影响宿主的免疫力和健康状况，包括癌症。有证据表明，微生物组改变与消化系统癌症之间存在生物学联系。已发现大肠杆菌和脆弱拟杆菌在由生殖系APC引起的家族性腺瘤性息肉病患者的结肠直肠黏膜组织中富集突变。此外，最近的研究发现某些口腔细菌、病毒和真菌在胃肠癌患者的肿瘤组织和粪便标本中富集。需要一种综合方法来阐明微生物在胃肠道癌症发病过程中的作用，该过程是通过肿瘤细胞中体细胞遗传和表观遗传改变的积累而发展的，受宿主遗传变异、免疫、微生物组和环境暴露的影响。分子病理流行病学 (MPE) 的跨学科领域提供了将生殖系遗传学和环境因素（包括饮食、生活方式和药理因素）与病理表型联系起来的研究框架。将微生物学整合到 MPE 模型 (microbiology-MPE) 有助于更好地理解环境、肿瘤细胞、免疫细胞和微生物组在各种疾病中的相互作用。我们回顾了有关微生物组的主要临床和实验研究，并描述了来自胃肠癌微生物学-MPE 研究的新证据。与基础实验研究一起，这种新的研究范式可以帮助我们通过靶向微生物组来开发新的胃肠道癌症预防和治疗策略。