Tian Tian, Zhao Yangzhi, Yang Yi, Wang Tiejun, Jin Shunzi, Guo Jie, Liu Zhongshan
Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University Changchun 130041, China.
Department of Hematology, The First Hospital of Jilin University Changchun 130021, China.
Am J Cancer Res. 2020 Nov 1;10(11):3508-3531. eCollection 2020.
A compelling set of links between chemotherapy- or radiation-induced intestinal inflammation and microbial dysbiosis has emerged. It is the proportional imbalance between pathogenic and beneficial bacteria that aggravates intestinal mucositis. Bacteria that ferment fibers and produce short-chain fatty acids (SCFAs), (such as acetate, propionate, and butyrate) are typically reduced in the mucosa and feces of patients undergoing cancer therapy. In contrast, increasing lipopolysaccharide-producing bacteria result in proinflammatory events by interacting with Toll-like receptors. A collective acceptance is that bacterial metabolites are critical in recovering intestinal homeostasis. We herein review evidence supporting the positive roles carried out by SCFAs. SCFAs, acting as signaling molecules, directly activate G-coupled-receptors and inhibit histone deacetylases. Thus, SCFAs are able to strengthen the gut barrier and regulate immunomodulatory functions. Furthermore, it is possible to reverse intestinal microbial dysbiosis and subsequently suppress the secretion of proinflammatory cytokines by directly applying SCFA-producing bacteria. In addition, anticancer effects of SCFAs have proved in the colorectal cancer. In this review, we discuss microbial dysbiosis and its impact on chemotherapy- or radiation-induced intestinal mucositis. Moreover, we summarize the mechanisms of SCFA production and its effects on intestinal mucositis. This review suggests the therapeutic potential of SCFAs for the management of chemotherapy- or radiation-induced intestinal inflammation.
化疗或放疗引起的肠道炎症与微生物群失调之间已出现一系列令人信服的联系。致病性细菌和有益细菌之间的比例失衡会加重肠道黏膜炎。在接受癌症治疗的患者的黏膜和粪便中，通常会减少发酵纤维并产生短链脂肪酸（如乙酸盐、丙酸盐和丁酸盐）的细菌。相反，产生脂多糖的细菌增多会通过与Toll样受体相互作用引发促炎事件。人们普遍认为细菌代谢产物对恢复肠道内环境稳定至关重要。我们在此回顾支持短链脂肪酸发挥积极作用的证据。短链脂肪酸作为信号分子，直接激活G偶联受体并抑制组蛋白脱乙酰酶。因此，短链脂肪酸能够加强肠道屏障并调节免疫调节功能。此外，直接应用产生短链脂肪酸的细菌有可能逆转肠道微生物群失调，进而抑制促炎细胞因子的分泌。此外，短链脂肪酸在结直肠癌中已被证明具有抗癌作用。在本综述中，我们讨论了微生物群失调及其对化疗或放疗引起的肠道黏膜炎的影响。此外，我们总结了短链脂肪酸的产生机制及其对肠道黏膜炎的影响。本综述提示了短链脂肪酸在治疗化疗或放疗引起的肠道炎症方面的潜在应用价值。
