Identifying microbial metabolites and the bacteria responsible for their formatio

识别微生物代谢物和负责其形成的细菌

基本信息

批准号：
8930930
负责人：
SYLVIA DUNCAN
金额：
$ 14.45万
依托单位：
UNIVERSITY OF ABERDEEN
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-22 至 2019-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Emerging evidence suggests that the gut microbiota play an important role in the development of many diseases including diabetes, cardiovascular disease and cancer. Despite tremendous advances in characterizing microbial diversity within the gastrointestinal tract, very little is known about their function and role of even the most dominant bacterial species within the human host. It is becoming widely accepted that the metabolic products formed by gut bacteria directly impact on human health and disease, particularly regarding immune response and inflammation. In most cases, the products of metabolism are uncharacterized and their mechanism of action unknown. To advance this area of research, this information is vital. This proposal will establish the link between microbial diversity and metabolic functionality by 1) identifying the microbial metabolites and their in vivo concentrations, 2) establishing their mechanism of formation and 3) characterizing the bacterial species responsible. It will deliver these results through a series of acute human interventions with well characterized substrates (macro-, micro- and non-nutrients quantitatively determined) and both the microbial population and metabolites produced identified. The mechanism of transformation and the bacteria responsible will be determined by in vitro incubations, again with well characterized substrates, key metabolites and a unique and comprehensive collection of microbial isolates. Finally, the inflammatory activity of the quantitatively identified metabolites will be established ex vivo. This investigation will deliver several important outcomes including: Identifying microbial metabolites which exhibit inflammatory activity at relevant in vivo concentrations. This will provide essential information (not currently available) informing wider studies looking at the action of microbial metabolites on particular receptors and biomarkers of health. Determining the bacterial species responsible, elucidating their potential function in the gut. Identification of keystone species with unique function will be a major focus and will allow us to identify extent of redundancy of certain species with regard to metabolite production. Established is the role of major macronutrients to drive microbial metabolism, both in the production of phytochemical metabolites and provision of carbohydrate/protein by-products. Only once the complex interplay between diet, the gut microbiota and human health is firmly established, will the role by which the gut microbiota contributes to maintenance of health or disease development be elucidated.

描述（由申请人提供）：新兴证据表明，肠道菌群在许多疾病的发展中起着重要作用，包括糖尿病，心血管疾病和癌症。尽管在胃肠道内表征微生物多样性方面取得了巨大进步，但对于人类宿主中最主要的细菌物种的功能和作用却很少。肠道细菌形成的代谢产物直接影响人类健康和疾病，尤其是在免疫反应和炎症方面，正被广泛接受。在大多数情况下，新陈代谢的产物未表征，其作用机理未知。为了推进这一研究领域，此信息至关重要。该建议将通过1）识别微生物代谢物及其体内建立微生物多样性与代谢功能之间的联系浓度，2）建立其形成机理和3）表征负责的细菌物种。它将通过一系列具有良好特征的底物（定量确定的宏观，微量和非营养素）以及所产生的微生物种群和代谢物的一系列急性人类干预措施（宏观，微量和非营养素）提供这些结果。转化的机理和负责的细菌将由体外孵育确定，再次具有表征良好的底物，关键代谢产物和独特而全面的微生物分离株。最后，定量鉴定的代谢产物的炎症活性将建立在体内。这项调查将带来一些重要的结果，包括：鉴定在相关体内浓度下表现出炎症活性的微生物代谢产物。这将提供基本信息（目前尚不可用），以了解微生物代谢产物对特定受体和健康生物标志物的作用。确定负责的细菌物种，阐明其潜在功能肠。具有独特功能的基石物种的识别将是一个主要重点，将使我们能够确定某些物种在代谢物生产方面的冗余程度。确定的是主要的大量营养素驱动微生物代谢的作用，包括生产植物化学代谢物以及碳水化合物/蛋白质副产品的提供。只有一旦饮食之间的复杂相互作用，肠道菌群和人类健康才能牢固确定，肠道微生物群的作用将有助于维持健康或疾病发展的作用。