Zhang Wanru, An Yaping, Qin Xiali, Wu Xuemei, Wang Xinyu, Hou Huiqin, Song Xueli, Liu Tianyu, Wang Bangmao, Huang Xuan, Cao Hailong
Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Front Oncol. 2021 Oct 18;11:739648. doi: 10.3389/fonc.2021.739648. eCollection 2021.
Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.
来自人体和动物模型研究的越来越多的证据表明，作为一个复杂生态系统的肠道微生物群对结直肠癌（CRC）起着至关重要的作用。经常报道的潜在机制强调特定病原体致癌活性的重要作用，但事实上，由外源性饮食底物或内源性宿主化合物产生的一系列代谢物同样占据着决定性地位。有害的肠道微生物群衍生代谢物，如氧化三甲胺、次级胆汁酸、硫化氢和N-亚硝基化合物，可重塑肠道微生物的生态组成和代谢活性，并形成一个易于受到致癌刺激的微环境。它们通过不同机制参与CRC的发生、发展和转移，包括诱导炎症和DNA损伤、激活致癌信号通路以及调节肿瘤免疫。在这篇综述中，我们主要总结了有害的肠道微生物群衍生代谢物与CRC之间的密切关系，并更新了关于CRC发病机制中有害代谢物的当前知识。然后，对针对这些代谢物进行CRC管理的多种干预措施进行了严格审查，包括饮食调节、益生菌/益生元、粪便微生物群移植，以及更精确的措施，如工程菌、噬菌体疗法和化学预防药物。更好地理解有害微生物代谢物与CRC之间的相互作用对对抗CRC具有很大的前景。
