Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science
Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science
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癌症作为微环境，系统和环境疾病：跨学科微生物科学的机会
DOI：
10.1136/gutjnl-2022-327209
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发表时间：
2022-07-12
期刊：
影响因子：
24.5
通讯作者：
Ogino, Shuji
中科院分区：
文献类型：
--
作者：
Inamura, Kentaro;Hamada, Tsuyoshi;Ogino, Shuji
癌症通常被认为是一种局部疾病，肿瘤微环境的作用已经确立。然而，癌症的领域超出了肿瘤微环境，癌症还应被视为一种全身性和环境性疾病。暴露（即暴露的总体），包括饮食、补充剂、吸烟、酒精、其他生活方式因素、药物等，可能会改变身体各个部位的微生物组（包括细菌、病毒、古菌、真菌、寄生虫等）和免疫系统，并影响肿瘤表型。全身代谢/炎症状态可能受到暴露和肠道生理变化的影响，可能影响结直肠和其他器官的组织微环境。生殖系基因组因子可以通过基因-环境相互作用改变疾病表型。尽管存在挑战，但至关重要的是，不仅要推进能够分析暴露、微生物和微环境成分对肿瘤进化影响的基础实验研究，还要推进能够剖析暴露体、微生物组和免疫组复杂致病作用的跨学科人群研究。宏基因组学、超转录组学和代谢组学分析应结合先进的人工智能和分子病理流行病学方法，融入精心设计的人口研究中。理想情况下，应该考虑在疾病检测前收集生物标本（如粪便）的前瞻性队列研究设计，以解决反向因果关系和回忆偏差。强大的实验和观察研究可以共同提供对致癌过程中环境暴露，微生物群，肿瘤和免疫之间动态相互作用的见解，从而帮助我们制定精确的预防和治疗策略，最终减少癌症负担。
Cancer is generally regarded as a localised disease, with the well-established role of the tumour microenvironment. However, the realm of cancer goes beyond the tumour microenvironment, and cancer should also be regarded as a systemic and environmental disease. The exposome (ie, the totality of exposures), which encompasses diets, supplements, smoking, alcohol, other lifestyle factors, medications, etc, likely alters the microbiome (inclusive of bacteria, viruses, archaea, fungi, parasites, etc) and immune system in various body sites and influences tumour phenotypes. The systemic metabolic/inflammatory status, which is likely influenced by exposures and intestinal physiological changes, may affect tissue microenvironment of colorectum and any other organs. Germline genomic factors can modify disease phenotypes via gene-by-environment interactions. Although challenges exist, it is crucial to advance not only basic experimental research that can analyse the effects of exposures, microorganisms and microenvironmental components on tumour evolution but also interdisciplinary human population research that can dissect the complex pathogenic roles of the exposome, microbiome and immunome. Metagenomic, metatranscriptomic and metabolomic analyses should be integrated into well-designed population research combined with advanced methodologies of artificial intelligence and molecular pathological epidemiology. Ideally, a prospective cohort study design that enables biospecimen (such as stool) collection before disease detection should be considered to address reverse causation and recall biases. Robust experimental and observational research together can provide insights into dynamic interactions between environmental exposures, microbiota, tumour and immunity during carcinogenesis processes, thereby helping us develop precision prevention and therapeutic strategies to ultimately reduce the cancer burden.