Effects of arylhydrocarbon receptor ligands 2,3,7,8-TCDD and dietary indole-3-carbinol on the gut microbiome, immune-mediated barrier function and metabolism
芳基烃受体配体 2,3,7,8-TCDD 和膳食吲哚-3-甲醇对肠道微生物组、免疫介导的屏障功能和代谢的影响
基本信息
- 批准号:376818135
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2017
- 资助国家:德国
- 起止时间:2016-12-31 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Adverse effects on the immune system and metabolism are characteristic harmful effects of dioxins and other so-called persistent organic pollutants (POPs). These pollutants are still present in the environment. POP pollution is of particular concern in developing countries, as appropriate emission control is often lacking. Dioxins bind to the endogenous transcription factor aryl hydrocarbon receptor (AHR), and thereby control cellular gene programs. The main route of exposure for dioxins is food. It is therefore surprising that very few studies exist which look at the effects of dioxin on the intestine and the intestinal immune system. Recent research using AHR-deficient mice has shown that the AHR is necessary for a functioning intestinal immune system and the balance of commensal versus pathogenic intestinal bacteria. Indeed, interest has increased dramatically in the microbiome as an important player in (gut) immunity and health. Activation of the AHR (e.g. by certain phytochemicals or products of by gut bacteria) prevent inflammatory processes. Lack of AHR or a lack of AHR ligands in the diet can lead to increased susceptibility to certain infections. Food ingredients are important to stimulate the AHR signaling and regulate the gut microbiome. In contrast, it is almost completely unknown whether and how dioxins and other persistent organic pollutants damage the gut microbiome, and thus might adversely affect gut immunity or metabolic health. We want to address this gap using the mouse model. We will examine for the first time which microbial changes are caused by dioxin exposure, and what consequences this has for immune barrier function and in the context of a Western-diet. We will furthermore establish and use a novel screening method by flow-cytometric measurements of microbiome patterns. Our results are (i) important for better risk assessment for dioxins themselves and other environmentally relevant AHR ligands, and (ii) for the approaches, using dietary AHR ligands to influence the gut microbiome, intestinal immune system, and metabolism positively.
对免疫系统和新陈代谢的不利影响是二恶英和其他所谓持久性有机污染物的典型有害影响。这些污染物仍然存在于环境中。持久性有机污染物污染在发展中国家尤其令人关切,因为它们往往缺乏适当的排放控制。二恶英与内源性转录因子芳烃受体(AHR)结合,从而控制细胞基因程序。二恶英的主要接触途径是食物。因此,令人惊讶的是,很少有研究着眼于二恶英对肠道和肠道免疫系统的影响。最近使用AHR缺陷小鼠的研究表明,AHR对于肠道免疫系统的功能以及肠道细菌与致病性肠道细菌的平衡是必需的。事实上,人们对微生物组作为(肠道)免疫和健康的重要参与者的兴趣急剧增加。AHR的激活(例如通过某些植物化学物质或肠道细菌的产物)防止炎症过程。饮食中缺乏AHR或缺乏AHR配体可导致对某些感染的易感性增加。食物成分对于刺激AHR信号传导和调节肠道微生物组很重要。相比之下,几乎完全不知道二恶英和其他持久性有机污染物是否以及如何损害肠道微生物组,从而可能对肠道免疫力或代谢健康产生不利影响。我们想用老鼠模型来解决这个问题。我们将首次研究二恶英暴露引起的微生物变化,以及这对免疫屏障功能和西方饮食的影响。我们将进一步建立和使用一种新的筛选方法,通过流式细胞术测量微生物组模式。我们的研究结果(i)对于更好地评估二恶英本身和其他环境相关的AHR配体的风险非常重要,(ii)对于使用饮食AHR配体积极影响肠道微生物组,肠道免疫系统和代谢的方法非常重要。
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)
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Professorin Dr. Charlotte Esser其他文献
Professorin Dr. Charlotte Esser的其他文献
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{{ truncateString('Professorin Dr. Charlotte Esser', 18)}}的其他基金
Arylhydrocarbon receptor dependent homeostasis and function of skin gamma-delta T cells
芳基烃受体依赖性稳态和皮肤 γ-δ T 细胞的功能
- 批准号:
267334553 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Research Grants
Role of the aryl hydrocarbon receptor in establishing oral tolerance
芳烃受体在建立口服耐受中的作用
- 批准号:
221398890 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
The functional role of aryl hydrocarbon receptor (AhR) in murine Langerhans cells: induction of indoleamine-2,3-dioxygenase (IDO) and adverse immunological consequnces
芳烃受体(AhR)在鼠朗格汉斯细胞中的功能作用:吲哚胺-2,3-双加氧酶(IDO)的诱导和不良免疫学后果
- 批准号:
210163833 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
The role of AHR for the gut-skin inflammatory axis
AHR 对肠-皮肤炎症轴的作用
- 批准号:
511936132 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Units
Role of the aryl hydrocarbon receptor in immunosurveillant functions of murine dendritic epidermal T cells
芳烃受体在鼠树突状表皮T细胞免疫监视功能中的作用
- 批准号:
493153656 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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Role of the arylhydrocarbon receptor in hepatic immune regulation
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Arylhydrocarbon receptor dependent homeostasis and function of skin gamma-delta T cells
芳基烃受体依赖性稳态和皮肤 γ-δ T 细胞的功能
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267334553 - 财政年份:2015
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Arylhydrocarbon receptor (AhR) and UVR-induced immunosuppression
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Transcriptional regulation mechanisms of arylhydrocarbon receptor(AhR), Arnt and E2F genes on proliferation process in A549 cells as promoter activity in carcinogenesis by dioxin
芳基烃受体(AhR)、Arnt和E2F基因对A549细胞增殖过程的转录调控机制作为二恶英致癌的促进剂活性
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Transcriptional regulation of arylhydrocarbon receptor (AhR), Arnt and E2F genes on proliferation process in A549 cells by dioxin and its mechanism.
二恶英对芳烃受体(AhR)、Arnt和E2F基因转录调控A549细胞增殖过程及其机制
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