The Role of Bile Salt Hydrolase in Glucose Metabolism

胆盐水解酶在葡萄糖代谢中的作用

基本信息

  • 批准号:
    10365160
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-01 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Currently, 34.2 million US adults, or approximately 10.3% of the total population, have diabetes. The prevalence of diabetes is two-fold higher among Veterans (20.5%) and it is the leading cause of kidney failure, lower-limb amputations, and adult-onset blindness both in Veterans and the general population. Over the last two decades, multiple metabolic studies have demonstrated that bile acids play an unexpected but important role in glucose homeostasis and metabolic syndrome. Correlational 16S and metagenomic studies suggest that gut microflora can affect host glucose homeostasis through modification of bile acids. The overall goal of this proposal is to determine the mechanisms by which the gut microflora affect host glucose homeostasis. To have a better functional understanding of this relationship, investigators need to assess the role of specific bacterial bile acid biotransformations and investigate their effects on the gut luminal ecology, the flux of metabolites and nutrients, and ultimately, physiology in conventionally-raised (as opposed to microbiome-depleted) hosts. Thus, there is a critical need for a tool that will facilitate knocking-in of specific bacterial functions into the gut microbiome and investigate their effects on the host glucose metabolism and insulin sensitivity. The investigators demonstrate an innovative strategy that addresses this need using engineered native bacteria. This novel approach allows quick and effective knocking-in of a beneficial function into the gut microbiome. The function is sustained, potentially for perpetuity, in conventionally-raised hosts with a single treatment and without the need for microbiome depletion. To date, the investigators have demonstrated that tractable native bacteria can be engineered to modify bile acids ex vivo, reintroduced to the host, engraft the entire gut, deliver an intended beneficial function, alter luminal and serum metabolites as intended, affect host metabolism, and even reverse disease. These functions affect host physiology and potentially alleviate disease. Using this new approach, the investigators will pursue the overall goal by addressing the central hypothesis that gut microbiome affects host insulin sensitivity through bile acid deconjugation and that these functions can be used to treat type 2 diabetes. In the next four years, the investigators will pursue the proposal's central hypothesis with three specific aims. The first aim will determine if bacterial bile acid deconjugation affects ileal and hepatic glucoregulatory transcripts in conventionally-raised C57Bl6 mice. Ultimately this aim will determine the relationship between bacterial bile acid modification and host bile acid signaling, gluconeogenesis, and incretin production. The second aim will determine if the glucoregulatory effects of microbial bile acid deconjugation are mediated by the farnesoid X receptor (FXR), a major bile acid receptor. This will be done using engineered native bacteria with and without BSH in FXR knockout mice. In the end, this aim will determine the importance of the role of FXR in mediating the metabolic effects of gut microbiome. The third aim will determine how diet affects the bacterial bile acid deconjugation influence on the host metabolic homeostasis, using both the diet-induced obesity model (which uses a high-fat diet) and ob/ob mice (which uses normal chow diet). Because bile acid signaling is heavily influenced by diet, this aim will further elucidate the relationship between bacterial bile acid modifications, nutrient intake, and host glucoregulatory response. The expected outcome of these studies is a better understanding of a) how the gut microbiome affects host glucose regulation and b) whether the gut microbiome can be manipulated to improve insulin sensitivity. The outcome will have a positive translational impact because it will lead to novel therapeutic targets to T2D using the signaling pathways and functions employed by the gut microbiome.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Amir Zarrinpar其他文献

Amir Zarrinpar的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Amir Zarrinpar', 18)}}的其他基金

Bacterial DNA as a Diagnostic Biomarker of Hepatocellular Carcinoma
细菌 DNA 作为肝细胞癌的诊断生物标志物
  • 批准号:
    10557105
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
The Role of Bile Salt Hydrolase in Glucose Metabolism
胆盐水解酶在葡萄糖代谢中的作用
  • 批准号:
    10617180
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Bacterial DNA as a Diagnostic Biomarker of Hepatocellular Carcinoma
细菌 DNA 作为肝细胞癌的诊断生物标志物
  • 批准号:
    10357369
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer
改造天然大肠杆菌来检测、报告和治疗结直肠癌
  • 批准号:
    10330342
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer
改造天然大肠杆菌来检测、报告和治疗结直肠癌
  • 批准号:
    10700076
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
  • 批准号:
    10273745
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
  • 批准号:
    10455260
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
  • 批准号:
    10217244
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
  • 批准号:
    10884617
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
  • 批准号:
    10456644
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了