Ethanol metabolizing Lactobacillus for cancer prevention

乙醇代谢乳酸菌预防癌症

• 批准号: 8305927
• 负责人: LIN TAO
• 金额: $ 7.97万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-26 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8305927
• 关键词: Acetaldehyde; Acetates; Adverse effects; Alcohol consumption; Alcohols; Animals; Applications Grants; Asians; Bacteria; Colon; Colon Carcinoma; Colorectal Cancer; Country; Data; Defect; Development; Diet; Dietary Component; Enzyme Kinetics; Enzymes; Escherichia coli; Esophagus; Ethanol; Ethanol Metabolism; Etiology; Exposure to; Funding; Gastrointestinal tract structure; Genes; Genetic; Genetic Polymorphism; Goals; Grant; Health; Human; Individual; Intestinal Cancer; Intestines; Isoenzymes; Knock-out; Lactobacillus; Lactobacillus casei rhamnosus; Lead; Link; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Methods; Mus; Mutate; Phenotype; Population; Prevention Research; Preventive; Probiotics; Prophylactic treatment; Risk; Risk Factors; Role; Source; Testing; Tumor Suppressor Genes; United States National Institutes of Health; Variant; Woman; acetaldehyde dehydrogenase; adenoma; anticancer research; base; cancer prevention; cancer risk; commensal microbes; dietary supplements; drinking water; malignant breast neoplasm; men; mortality; mouse model; mutant; novel; prevent; programs; response; tumorigenesis

DESCRIPTION (provided by applicant): Ethanol metabolizing Lactobacillus for cancer prevention. Mortality from colorectal cancer (CRC) is second only to that from lung cancer in men and breast cancer in women. Ethanol consumption is a well known risk factor for CRC. Recently, the host ethanol metabolism gene polymorphism has been linked to increased risks of ethanol-associated cancers, mainly esophageal cancer, but also to a lesser degree CRC. Unlike the esophagus, the colon is filled with trillions of bacteria that metabolize ethanol to carcinogenc acetaldehyde. The commensal bacterium Lactobacillus rhamnosus GG has been used for nearly three decades to promote the digestive health and to prevent CRC. However, this bacterium does not metabolize ethanol and thus might have a limited effect against ethanol-associated CRC. By analyzing commensal bacteria for ethanol metabolism we have isolated two L. rhamnosus strains that metabolize ethanol to acetate. These strains not only have all the probiotic benefits of L. rhamnosus GG, but they can also eliminate ethanol and its carcinogenic metabolite acetaldehyde from the host intestine. We hypothesize that ethanol metabolizing L. rhamnosus can reduce the risk of ethanol-associated cancers in the gut. We will pursue two specific aims: (i) study L. rhamnosus genes encoding ethanol metabolism; and (ii) test L. rhamnosus for inhibition of ethanol-associated gut tumorigenesis in mice. Because L. rhamnosus GG has shown some effect against ethanol-unassociated CRC in animals and humans, the proposed study with an ethanol-metabolizing L. rhamnosus will likely lead to the development of a more effective prophylaxis against both ethanol-associated and ethanol-unassociated CRC. PUBLIC HEALTH RELEVANCE: It has been well established that consistent alcohol consumption doubles the risk for colon cancer, but current cancer preventive methods, such as the dietary supplement made with probiotic Lactobacillus, do not eliminate alcohol and therefore have a limited effect against alcohol-associated colon cancer. We propose to study an alcohol-metabolizing probiotic Lactobacillus, which will likely lead to the development of a novel, more effective prophylaxis against both alcohol-associated and alcohol- unassociated colon cancer.

描述（由申请人提供）：乙醇代谢乳杆菌预防癌症。 结直肠癌（CRC）的死亡率仅次于女性的男性和乳腺癌的肺癌。乙醇消耗是CRC的众所周知的危险因素。最近，宿主乙醇代谢基因多态性与增加乙醇相关癌症的风险增加有关，主要是食管癌，但也较小。与食道不同，结肠充满了数万亿的细菌，这些细菌将乙醇代谢为癌乙醛。共生细菌乳杆菌GG已使用了近三十年来促进消化健康并预防CRC。但是，该细菌不会代谢乙醇，因此可能对与乙醇相关的CRC产生有限的作用。通过分析乙醇代谢的共生细菌，我们分离了两个将乙醇代谢为乙酸盐的鼠李乳杆菌菌株。这些菌株不仅具有R. rhamnosus gg的所有益生菌益处，而且还可以消除乙醇及其致癌代谢物乙醛的乙醇。我们假设乙醇代谢鼠李乳杆菌可以降低肠道中与乙醇相关的癌症的风险。我们将追求两个具体的目标：（i）研究编码乙醇代谢的鼠李乳杆菌基因； （ii）鼠李乳杆菌测试小鼠抑制与乙醇相关的肠肿瘤发生的。由于R. rhamnosus gg在动物和人类中对与乙醇无关的CRC显示出一定作用，因此提出的使用乙醇 - 代谢的鼠李糖乳杆菌的研究可能会导致对乙醇相关和与乙醇相关和与乙醇无关的CRC产生更有效的预防。 公共卫生相关性：已经有很好的确定，一致的饮酒量增加了结肠癌的风险，但是当前的癌症预防方法，例如用益生菌乳酸乳杆菌制成的饮食补充剂，并不能消除酒精，因此对与酒精相关的结肠癌的影响有限。我们建议研究一种酒精代谢的益生菌乳酸杆菌，这可能会导致针对酒精相关和非相关结肠癌的新型，更有效的预防。