C ALBICANS IN THE GI TRACT ENVIRONMENT

本研究项目探讨了白色念珠菌细胞定植与胃肠道环境的相互作用。胃肠道内白色念珠菌的定植对人类来说很常见，一般不会对人类健康造成不利影响。然而，如果患者的免疫功能受损，定植的白色念珠菌细胞可能会逃脱胃肠道，进入血流，导致播散性疾病。因此，GI的定植意义重大，因为致病真菌细胞产生于将宿主定植为无害共生体的种群。此外，初步结果表明，在一定条件下，白色念珠菌的定植增加了宿主对肠道细菌病原体致死攻击的抵抗力。这项拟议研究的长期目标是了解白色念珠菌改变胃肠道环境并影响宿主对挑战的抵抗力的机制。具体目标1的重点是确定对抗菌化合物解毒的白色念珠菌活性。在具体目标2中，目标是了解白色念珠菌如何改变胃肠道的代谢物环境。在《特定目标3》中提出的研究将分析白色念珠菌的影响。 肠道微生物区系组成上的定殖化。这些研究将增加对白色念珠菌和哺乳动物胃肠道环境之间相互作用的理解。更深入的了解将有助于开发新的干预措施，利用胃肠道白色念珠菌的有益影响。

This research project investigates the interactions between colonizing Candida albicans cells and the GI tract environment. GI colonization with C. albicans is common for humans and generally does not have adverse effects on human health. However, if a patient becomes immunocompromised, colonizing C. albicans cells can escape the GI tract, reach the blood stream and cause disseminated disease. GI colonization is therefore significant because disease-causing fungal cells arise from the populations that colonize the host as harmless commensals. In addition, preliminary results show that, under certain conditions, colonization with C. albicans increases the resistance of the host to lethal challenge with an enteric bacterial pathogen. The long term goals of the proposed research are to understand the mechanisms by which C. albicans alters the GI tract environment and affects host resistance to challenge. The focus of Specific Aim 1 is to identify C. albicans activities that detoxify antimicrobial compounds. In Specific Aim 2, the goal is to understand how C. albicans alters the metabolite milieu of the GI tract. The studies proposed in Specific Aim 3 will analyze the effects of C. albicans colonization on the composition of the gut microbiota. These studies will increase the understanding of the interplay between C. albicans and the mammalian GI tract environment. Deeper understanding will enable development of novel interventions that harness the beneficial effects of C. albicans in the GI tract.