Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China.
Food Funct. 2020 Nov 18;11(11):10070-10083. doi: 10.1039/d0fo01944e.
Epidemiologic evidence suggests that riboflavin (RBF) deficiency is a specific nutritional predisposition for esophageal cancer. The aim of this study is to investigate the potential roles of gut microbiota in esophageal tumorigenesis caused by the RBF deficiency.
Male F344 rats were subcutaneously injected with the chemical carcinogen N-nitrosomethylbenzylamine (NMBA, 0.35 mg kg-1). Rats were assigned to 4 groups, denoted as R6 (normal RBF, 6 mg kg-1), R6N (normal RBF combined with NMBA), R6N → R0N (normal RBF conversion to RBF-deficiency), and R0N → R6N (RBF-deficiency conversion to normal RBF). Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Oxidative DNA damage and double-strand break markers were studied by immunohistochemistry.
The R6N → R0N diet enhanced the incidence of esophageal intraepithelial neoplasia (EIN, 40 weeks 66.7% vs. 25 weeks 16.7%, P < 0.05). RBF deficiency and replenishment modulated the gut microbiota composition. The gut microbiota (e.g. Caulobacteraceae, Sphingomonas and Bradyrhizobium) affected xenobiotic biodegradation and the genomic instability of the host. Furthermore, the RBF deficiency aggravated oxidative DNA damage and DNA double-strand breaks (immunohistochemistry) in the esophageal epithelium, whereas the RBF replenishment had the opposite effect (P < 0.05, respectively).
RBF deficiency promotes NMBA-induced esophageal tumorigenesis, which is associated with gut microbiota-associated genomic instability, and offers new insights into the role of RBF deficiency in esophageal carcinogenesis.
流行病学证据表明，核黄素（RBF）缺乏是食管癌的一种特定营养易感性。本研究旨在探讨肠道微生物群在 RBF 缺乏引起的食管肿瘤发生中的潜在作用。
雄性 F344 大鼠皮下注射化学致癌物 N-亚硝基甲基苄胺（NMBA，0.35mgkg-1）。将大鼠分为 4 组，分别表示为 R6（正常 RBF，6mgkg-1）、R6N（正常 RBF 结合 NMBA）、R6N→R0N（正常 RBF 转化为 RBF 缺乏）和 R0N→R6N（RBF 缺乏转化为正常 RBF）。基于高通量 16S rRNA 基因测序分析细菌群落。通过免疫组织化学研究氧化 DNA 损伤和双链断裂标志物。
R6N→R0N 饮食增强了食管上皮内瘤变（EIN，40 周 66.7%比 25 周 16.7%，P<0.05）的发生率。RBF 缺乏和补充调节了肠道微生物群落组成。肠道微生物群（例如，Caulobacteraceae、Sphingomonas 和 Bradyrhizobium）影响外来生物的生物降解和宿主的基因组不稳定性。此外，RBF 缺乏加重了食管上皮中的氧化 DNA 损伤和 DNA 双链断裂（免疫组织化学），而 RBF 补充则有相反的效果（分别为 P<0.05）。
RBF 缺乏促进 NMBA 诱导的食管肿瘤发生，这与肠道微生物群相关的基因组不稳定性有关，为 RBF 缺乏在食管癌变中的作用提供了新的见解。
