Department of Surgery, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-ku, Kumamoto, 860-0008, Japan.
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hum Genet. 2021 May;140(5):725-746. doi: 10.1007/s00439-020-02235-2. Epub 2020 Nov 12.
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.
基于下一代测序技术的宏基因组学研究揭示了丰富的人类肠道微生物组，其可能影响宿主免疫和健康状况，包括癌症。有证据表明，微生物组的改变与消化系统癌症之间存在生物学联系。在由种系 APC 突变引起的家族性腺瘤性息肉病患者的结直肠黏膜组织中，已发现大肠杆菌和脆弱拟杆菌增多。此外，最近的研究发现，胃肠道癌症患者的肿瘤组织和粪便标本中某些口腔细菌、病毒和真菌的丰度增加。需要采用综合方法来阐明微生物在胃肠道癌症发病机制中的作用，这些癌症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研究框架，将种系遗传学和环境因素（包括饮食、生活方式和药理学因素）与病理表型联系起来。将微生物学纳入 MPE 模型（微生物学-MPE）可以帮助更好地理解环境、肿瘤细胞、免疫细胞和微生物组在各种疾病中的相互作用。我们综述了关于微生物组的主要临床和实验研究，并描述了来自胃肠道癌症微生物学-MPE 研究的新证据。结合基础实验研究，这一新的研究范式可以帮助我们通过靶向微生物组来开发胃肠道癌症的新的预防和治疗策略。
