Effect of the gut microbiota on malaria

肠道微生物群对疟疾的影响

• 批准号: 8969160
• 负责人: Nathan Schmidt
• 金额: $ 8.49万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8969160
• 关键词: Effect; gut; microbiota; malaria

DESCRIPTION (provided by applicant): Plasmodium infections, which cause malaria, have been a scourge to humanity for thousands of years. Unfortunately, we are still years away from an efficacious anti-malaria vaccine that is available to the >40% of the world's population that is at risk of malaria. Further complicating treatment and control of malaria is that both Plasmodium and the mosquito vector that transmits the parasite rapidly develop resistance to new drugs developed to treat malaria and control mosquito populations. Therefore, it is imperative novel approaches to control malaria are explored. We propose an exploratory project to determine the impact of the gut microbiota on regulating the severity of malaria, which has the potential to provide insights to novel and affordable approaches to treat malaria. The gut microbiota has been shown to shape susceptibility to obesity, diabetes, and regulate multiple aspects of host immunity. This is particularly true for components of the immune system that interface with the GI tract. Importantly, the gut microbiota also augments host immunity to bacterial and viral infections that occur outside of the GI tract. However, there are no reports as to how the gut microbiota influence host immune responses to non-GI tract parasitic infections, including Plasmodium. Our preliminary data demonstrate that C57BL/6 mice purchased from different vendors, which are known to have alterations in their gut microbiota, exhibit substantially different levels of parasite burden following infection with Plasmodium yoelii 17XNL. We have also demonstrated that C57BL/6 mice from different vendors treated with a cocktail of antibiotics exhibit dynamic responses following infection with Plasmodium compared to control treated mice. Collectively, our data suggest the gut microbiota regulates the severity of malaria. We hypothesize that specific gut bacteria and their metabolic by-products regulate susceptibility to malaria. We will address this hypothesis through the following specific aims: 1) Identify differences in gut microbiota populations that are associated with differential susceptibility to malaria, 2) Determine ability of the gut microbiota to transfer resistance or susceptibility to malaria to another mouse and 3) Identify gut metabolites that drive differential susceptibility to malaria.

描述(申请人提供)：疟原虫感染，导致疟疾，数千年来一直是人类的祸害。不幸的是，我们仍需数年时间才能研制出有效的抗疟疾疫苗，使全世界40%的人口都能获得。 有患疟疾的危险。使疟疾的治疗和控制进一步复杂化的是，疟原虫和传播寄生虫的蚊子媒介对治疗疟疾和控制蚊子种群的新药迅速产生抗药性。因此，迫切需要探索控制疟疾的新方法。我们提出了一个探索性项目，以确定肠道微生物区系对调节疟疾严重程度的影响，这有可能为治疗疟疾的新的和负担得起的方法提供见解。肠道微生物区系已被证明形成对肥胖、糖尿病的易感性，并调节宿主免疫的多个方面。对于与胃肠道相连的免疫系统的组成部分来说尤其如此。重要的是，肠道微生物区系还增强了宿主对发生在胃肠道外的细菌和病毒感染的免疫力。然而，目前还没有关于肠道微生物区系如何影响宿主对包括疟原虫在内的非胃肠道寄生虫感染的免疫反应的报道。我们的初步数据显示，从不同供应商购买的C57BL/6小鼠在感染约氏疟原虫17XNL后，表现出显著不同水平的寄生虫负担。我们还证明，与对照组相比，来自不同供应商的C57BL/6小鼠在接受抗生素鸡尾酒治疗后，在感染疟原虫后表现出动态反应。总的来说，我们的数据表明，肠道微生物区系调节着疟疾的严重程度。我们假设，特定的肠道细菌及其代谢副产物调节疟疾的易感性。我们将通过以下具体目标来解决这一假说：1)确定与疟疾不同易感性相关的肠道微生物群的差异，2)确定肠道微生物群将对疟疾的抵抗力或敏感性转移到另一只小鼠的能力，以及3)确定驱动疟疾不同易感性的肠道代谢物。