Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Department of Internal Medicine, Scripps Mercy Hospital, San Diego, CA 92103, USA.
Int J Mol Sci. 2024 Aug 20;25(16):9026. doi: 10.3390/ijms25169026.
Colorectal cancer (CRC) continues to be a significant contributor to global morbidity and mortality. Emerging evidence indicates that disturbances in gut microbial composition, the formation of reactive oxygen species (ROS), and the resulting inflammation can lead to DNA damage, driving the pathogenesis and progression of CRC. Notably, bacterial metabolites can either protect against or contribute to oxidative stress by modulating the activity of antioxidant enzymes and influencing signaling pathways that govern ROS-induced inflammation. Additionally, microbiota byproducts, when supplemented through probiotics, can affect tumor microenvironments to enhance treatment efficacy and selectively mediate the ROS-induced destruction of CRC cells. This review aims to discuss the mechanisms by which taxonomical shifts in gut microbiota and related metabolites such as short-chain fatty acids, secondary bile acids, and trimethylamine-N-oxide influence ROS concentrations to safeguard or promote the onset of inflammation-mediated CRC. Additionally, we focus on the role of probiotic species in modulating ROS-mediated signaling pathways that influence both oxidative status and inflammation, such as Nrf2-Keap1, NF-κB, and NLRP3 to mitigate carcinogenesis. Overall, a deeper understanding of the role of gut microbiota on oxidative stress may aid in delaying or preventing the onset of CRC and offer new avenues for adjunct, CRC-specific therapeutic interventions such as cancer immunotherapy.
结直肠癌(CRC)仍然是全球发病率和死亡率的重要原因。新出现的证据表明,肠道微生物组成的紊乱、活性氧(ROS)的形成以及由此产生的炎症会导致 DNA 损伤,从而驱动 CRC 的发病机制和进展。值得注意的是,细菌代谢物可以通过调节抗氧化酶的活性和影响控制 ROS 诱导炎症的信号通路,来防止或促进氧化应激。此外,通过益生菌补充微生物副产物可以影响肿瘤微环境,以提高治疗效果并选择性地介导 CRC 细胞中 ROS 诱导的破坏。本综述旨在讨论肠道微生物群落的分类变化以及相关代谢物(如短链脂肪酸、次级胆汁酸和三甲胺-N-氧化物)如何影响 ROS 浓度以保护或促进炎症介导的 CRC 的发生的机制。此外,我们还重点关注益生菌物种在调节 ROS 介导的信号通路中的作用,这些信号通路影响氧化状态和炎症,如 Nrf2-Keap1、NF-κB 和 NLRP3,以减轻癌变。总的来说,深入了解肠道微生物群在氧化应激中的作用可能有助于延迟或预防 CRC 的发生,并为癌症免疫疗法等辅助性、CRC 特异性治疗干预提供新的途径。
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