Ethanol metabolizing Lactobacillus for cancer prevention

乙醇代谢乳酸菌预防癌症

基本信息

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
项目类别：
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

项目摘要

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）：用于预防癌症的乙醇代谢乳杆菌。结直肠癌（CRC）的死亡率仅次于男性肺癌和女性乳腺癌。乙醇消耗是众所周知的结直肠癌危险因素。最近，宿主乙醇代谢基因多态性与乙醇相关癌症（主要是食道癌）的风险增加有关，但也与较小程度的结直肠癌有关。与食道不同，结肠充满了数万亿细菌，这些细菌将乙醇代谢为致癌物乙醛。近三十年来，共生细菌鼠李糖乳杆菌 GG 一直被用于促进消化系统健康和预防结直肠癌。然而，这种细菌不代谢乙醇，因此对乙醇相关结直肠癌的作用可能有限。通过分析共生细菌的乙醇代谢，我们分离出两种将乙醇代谢为乙酸的鼠李糖乳杆菌菌株。这些菌株不仅具有鼠李糖乳杆菌 GG 的所有益生菌功效，而且还可以从宿主肠道中消除乙醇及其致癌代谢物乙醛。我们假设乙醇代谢鼠李糖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目标：（i）研究编码乙醇代谢的鼠李糖乳杆菌基因； (ii) 测试鼠李糖乳杆菌对小鼠乙醇相关肠道肿瘤发生的抑制作用。由于鼠李糖乳杆菌 GG 在动物和人类中显示出对与乙醇无关的 CRC 有一定作用，因此拟议的利用乙醇代谢鼠李糖乳杆菌的研究可能会导致开发出针对乙醇相关和乙醇非相关的更有效的预防方法CRC。公众健康相关性：众所周知，持续饮酒会使患结肠癌的风险加倍，但目前的癌症预防方法，例如用益生菌乳酸菌制成的膳食补充剂，并不能消除酒精，因此对与酒精相关的疾病的效果有限。结肠癌。我们建议研究一种酒精代谢益生菌乳杆菌，这可能会导致开发出一种新颖的、更有效的预防酒精相关和酒精无关结肠癌的方法。