Department of Radiation Oncology, First Bethune Hospital of Jilin University, ChangChun, China.
Orthopedic Medical Center, The Second Hospital of Jilin University, ChangChun, China.
Adv Nutr. 2019 Jan 1;10(1):133-147. doi: 10.1093/advances/nmy076.
Chemotherapy- or radiotherapy-related intestinal microbial dysbiosis is one of the main causes of intestinal mucositis. Cases of bacterial translocation into peripheral blood and subsequent sepsis occur as a result of dysfunction in the intestinal barrier. Evidence from recent studies depicts the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis, which creates an imbalance between beneficial and harmful bacteria in the gut. Decreases in beneficial bacteria can lead to a weakening of the resistance of the gut to harmful bacteria, resulting in robust activation of proinflammatory signaling pathways. For example, lipopolysaccharide (LPS)-producing bacteria activate the nuclear transcription factor-κB signaling pathway through binding with Toll-like receptor 4 on stressed epithelial cells, subsequently leading to secretion of proinflammatory cytokines. Nevertheless, various studies have found that the omega-3 (n-3) polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid and eicosapentaenoic acid can reverse intestinal microbial dysbiosis by increasing beneficial bacteria species, including Lactobacillus, Bifidobacterium, and butyrate-producing bacteria, such as Roseburia and Coprococcus. In addition, the n-3 PUFAs decrease the proportions of LPS-producing and mucolytic bacteria in the gut, and they can reduce inflammation as well as oxidative stress. Importantly, the n-3 PUFAs also exert anticancer effects in colorectal cancers. In this review, we summarize the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis and introduce the contributions of dysbiosis to the pathogenesis of intestinal mucositis. Next, we discuss how n-3 PUFAs could alleviate chemotherapy- or radiotherapy-related intestinal microbial dysbiosis. This review provides new insights into the clinical administration of n-3 PUFAs for the management of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis.
化疗或放疗相关的肠道微生物失调是肠道黏膜炎的主要原因之一。由于肠道屏障功能障碍,细菌易位进入外周血并随后发生败血症。最近的研究证据描述了化疗或放疗相关的肠道微生物失调的特征,这种失调导致肠道内有益菌和有害菌之间失去平衡。有益菌的减少会导致肠道对有害菌的抵抗力减弱,从而导致促炎信号通路的强烈激活。例如,产生脂多糖(LPS)的细菌通过与应激上皮细胞上的 Toll 样受体 4 结合,激活核转录因子-κB 信号通路,随后导致促炎细胞因子的分泌。然而,各种研究发现,ω-3(n-3)多不饱和脂肪酸(PUFAs),如二十二碳六烯酸和二十碳五烯酸,可以通过增加有益菌的种类来逆转肠道微生物失调,包括乳杆菌、双歧杆菌和丁酸产生菌,如罗斯伯里氏菌和粪球菌。此外,n-3 PUFAs 减少了肠道中 LPS 产生菌和黏液溶解菌的比例,它们可以减轻炎症和氧化应激。重要的是,n-3 PUFAs 对结直肠癌也具有抗癌作用。在这篇综述中,我们总结了化疗或放疗相关的肠道微生物失调的特征,并介绍了失调对肠道黏膜炎发病机制的贡献。接下来,我们讨论了 n-3 PUFAs 如何缓解化疗或放疗相关的肠道微生物失调。这篇综述为临床应用 n-3 PUFAs 管理化疗或放疗相关的肠道微生物失调提供了新的见解。