Department of Pathology and Mary H. Weiser Food Allergy Center, Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Gut Liver. 2023 Mar 15;17(2):190-203. doi: 10.5009/gnl220260. Epub 2023 Jan 12.
The global burden of colorectal cancer (CRC) is expected to continuously increase. Through research performed in the past decades, the effects of various environmental factors on CRC development have been well identified. Diet, the gut microbiota and their metabolites are key environmental factors that profoundly affect CRC development. Major microbial metabolites with a relevance for CRC prevention and pathogenesis include dietary fiber-derived short-chain fatty acids, bile acid derivatives, indole metabolites, polyamines, trimethylamine-N-oxide, formate, and hydrogen sulfide. These metabolites regulate various cell types in the intestine, leading to an altered intestinal barrier, immunity, chronic inflammation, and tumorigenesis. The physical, chemical, and metabolic properties of these metabolites along with their distinct functions to trigger host receptors appear to largely determine their effects in regulating CRC development. In this review, we will discuss the current advances in our understanding of the major CRC-regulating microbial metabolites, focusing on their production and interactive effects on immune responses and tumorigenesis in the colon.
预计全球结直肠癌(CRC)的负担将持续增加。通过过去几十年的研究,已经充分确定了各种环境因素对 CRC 发展的影响。饮食、肠道微生物群及其代谢物是对 CRC 发展有深远影响的关键环境因素。与 CRC 预防和发病机制相关的主要微生物代谢物包括膳食纤维衍生的短链脂肪酸、胆汁酸衍生物、吲哚代谢物、多胺、氧化三甲胺、甲酸和硫化氢。这些代谢物调节肠道中的各种细胞类型,导致肠道屏障、免疫、慢性炎症和肿瘤发生改变。这些代谢物的物理、化学和代谢特性以及它们触发宿主受体的不同功能似乎在很大程度上决定了它们在调节 CRC 发展中的作用。在这篇综述中,我们将讨论目前对主要 CRC 调节微生物代谢物的理解进展,重点讨论它们在结肠中的产生及其对免疫反应和肿瘤发生的相互作用。