Ethanol metabolizing Lactobacillus for cancer prevention

描述（由申请人提供）：用于预防癌症的乙醇代谢乳酸杆菌。 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CRC的一个众所周知的风险因素。最近，宿主乙醇代谢基因多态性与乙醇相关癌症的风险增加有关，主要是食管癌，但也有较小程度的CRC。与食道不同，结肠充满了数万亿的细菌，它们将乙醇代谢成致癌物质乙醛。近三十年来，鼠李糖乳杆菌GG一直被用于促进消化系统健康和预防CRC。然而，这种细菌不代谢乙醇，因此可能对乙醇相关的CRC的作用有限。通过对酿酒细菌乙醇代谢的分析，我们分离到两株L.将乙醇代谢成乙酸盐的鼠李糖酵母菌株。这些菌株不仅具有L.鼠李糖酵母GG，但他们也可以消除乙醇及其致癌代谢物乙醛从宿主肠道。我们推测，乙醇代谢L。鼠李糖可以降低肠道中乙醇相关癌症的风险。我们将追求两个具体目标：（一）研究L。rhamnosus基因编码乙醇代谢;和（ii）测试L. rhamnosus用于抑制小鼠中乙醇相关的肠道肿瘤发生。因为L. rhamnosus GG在动物和人类中显示出对乙醇无关CRC的一些作用，用乙醇代谢L. rhamnosus可能会导致开发一种更有效的预防乙醇相关和乙醇无关的CRC。

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.