Elucidating the consequences of dietary sugar consumption on the gut microbiota
阐明膳食糖消耗对肠道微生物群的影响
基本信息
- 批准号:10658136
- 负责人:
- 金额:$ 59.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:Autoimmune DiseasesBacteroidesBacteroides thetaiotaomicronBacteroidetesBindingCarbohydratesColitisColorectal CancerConsumptionDevelopmentDietDietary SugarsDiseaseDisease susceptibilityDistalExhibitsFructoseFucoseGene ExpressionGenesGenetic TranscriptionGlucoseGrowthHealthHomologous GeneHumanImmune systemIn VitroIndividualIndustrializationInflammatory Bowel DiseasesInsulinaseIntestinesLigandsMammalsMediatingMetabolicMetabolismModernizationMolecularMolecular TargetMusPathogenesisPathway interactionsPeptide HydrolasesPhysiologyPolysaccharidesPopulationPredispositionProcessProteinsReducing dietRegulatory T-LymphocyteReporterRodent ModelRoleSignal PathwaySignal TransductionT cell differentiationThinnessWorkabsorptioncommensal bacteriadietaryfitnessgut bacteriagut colonizationgut inflammationgut microbesgut microbiotahost microbiotahost-microbe interactionshuman diseaseimmunoregulationin vivometabolomicsmicrobialmicrobial productsmutantnon-alcoholic fatty liver diseasenovelresponsesugartranscription factortranscriptomics
项目摘要
Project Summary
The gut microbiota is a critical determinant of human health and development. Diets rich in the refined sugars
glucose and fructose can modulate gut microbial abundance and metabolism thereby increasing disease
susceptibility. However, the mechanisms governing microbial responses to dietary sugar in the gut remain poorly
understood. We have demonstrated that host dietary sugar consumption silences expression of a colonization
factor called Roc in Bacteroides thetaiotaomicron, an abundant gut bacterium associated with lean, healthy
individuals. We determined that a conserved transcription factor is necessary to synthesize Roc and regulates
additional bacterial factors that mediate critical host-microbial interactions, including an immunomodulatory
protein and fucose utilization genes. We hypothesize that the activity of this transcription factor is governed by a
putative intracellular metabolite that is differentially synthesized according to host diet composition and
dramatically reduced upon sugar-rich diet consumption. We have identified critical molecular players governing
the activity of this transcription factor and propose to 1.) elucidate the mechanisms governing its activation, 2.)
determine how dietary sugar consumption silences its activity, and 3.) characterize the consequences of host
sugar-rich diet consumption on microbial product synthesis in vivo. We believe that this work will reveal a
conserved pathway that is disrupted by host sugar consumption resulting in aberrant gut microbial activities.
Furthermore, this work has uncovered a molecular target for modulation of microbial abundance and metabolism
in the host and can be exploited for rational manipulation of the gut microbiota to treat diseases.
项目概要
肠道微生物群是人类健康和发育的关键决定因素。富含精制糖的饮食
葡萄糖和果糖可以调节肠道微生物丰度和代谢,从而增加疾病的发生
易感性。然而,控制肠道微生物对膳食糖的反应的机制仍然很差
明白了。我们已经证明,宿主饮食中的糖消耗会抑制定植的表达
Bacteroides thetaiotaomicron 中名为 Roc 的因子,这是一种丰富的肠道细菌,与瘦身、健康有关
个人。我们确定保守的转录因子是合成 Roc 所必需的并调节
介导关键宿主-微生物相互作用的其他细菌因素,包括免疫调节剂
蛋白质和岩藻糖利用基因。我们假设该转录因子的活性受
根据宿主饮食成分不同合成的推定细胞内代谢物
显着减少富含糖的饮食消耗。我们已经确定了控制的关键分子参与者
该转录因子的活性,并提出 1.) 阐明控制其激活的机制,2.)
确定膳食糖消耗如何抑制其活性,以及 3.) 表征宿主的后果
富含糖的饮食消耗对体内微生物产物合成的影响。我们相信这项工作将揭示
保守的途径被宿主糖消耗破坏,导致肠道微生物活动异常。
此外,这项工作发现了调节微生物丰度和代谢的分子靶标
在宿主体内,可用于合理控制肠道微生物群以治疗疾病。
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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Guy Edmund Townsend其他文献
Guy Edmund Townsend的其他文献
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{{ truncateString('Guy Edmund Townsend', 18)}}的其他基金
Harnessing the gut microbiome to detect and quantify glycans
利用肠道微生物组来检测和量化聚糖
- 批准号:
10501753 - 财政年份:2022
- 资助金额:
$ 59.1万 - 项目类别:
Harnessing the gut microbiome to detect and quantify glycans
利用肠道微生物组来检测和量化聚糖
- 批准号:
10693304 - 财政年份:2022
- 资助金额:
$ 59.1万 - 项目类别:
Harnessing the gut microbiome to detect and quantify glycans
利用肠道微生物组来检测和量化聚糖
- 批准号:
10798384 - 财政年份:2022
- 资助金额:
$ 59.1万 - 项目类别:
High-throughput surveillance of gut mucosal polysaccharides
肠粘膜多糖的高通量监测
- 批准号:
10092948 - 财政年份:2020
- 资助金额:
$ 59.1万 - 项目类别:
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