Ethanol metabolizing Lactobacillus for cancer prevention

描述(申请人提供)：酒精代谢乳酸菌用于癌症预防。结直肠癌死亡率仅次于男性肺癌和女性乳腺癌。乙醇消费是结直肠癌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，主要是食道癌，但也与较小程度的结直肠癌有关。与食道不同，结肠充满了数以万亿计的细菌，这些细菌将乙醇代谢成致癌的乙醛。共生细菌鼠李糖乳杆菌GG已用于促进消化健康和预防结直肠癌，已有近30年的历史。然而，这种细菌不代谢乙醇，因此可能对乙醇相关的结直肠癌有有限的影响。通过对乙醇代谢共生菌的分析，我们分离到了两株能将乙醇代谢成乙酸酯的鼠李糖菌株。这些菌株不仅具有鼠李糖GG的所有益生菌益处，而且还能从宿主肠道中清除乙醇及其致癌代谢物乙醛。我们假设乙醇代谢鼠李糖可以降低与乙醇相关的肠道癌症的风险。我们将追求两个特定的目标：(I)研究鼠李糖编码乙醇代谢的基因；(Ii)测试鼠李糖对乙醇相关小鼠肠道肿瘤发生的抑制作用。由于鼠李糖GG在动物和人类中对乙醇非相关性结直肠癌有一定的抑制作用，因此对乙醇代谢的鼠李糖进行的研究可能会导致开发一种更有效的预防乙醇相关和乙醇非相关性结直肠癌的方法。

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.