Obesogenic diet-induced intestinal epithelium repair responses link dysbiosis and cardiovascular disease

肥胖饮食诱导的肠上皮修复反应将生态失调与心血管疾病联系起来

基本信息

项目摘要

PROJECT SUMMARY An obesogenic Western-style (HF) diet causes low-grade intestinal inflammation, intestinal microbiota imbalance, and an increased risk of cardiovascular disease. However, our knowledge about the pathways producing each of these different disease manifestations is incomplete, making it difficult to see connections. Experiments proposed in this application are aimed at addressing this critical gap in knowledge. Our long-range goal is to elucidate molecular mechanisms that make the gut microbiota a liability during non-communicable diseases. This application aims to study the mechanisms through which HF diet drives gut dysbiosis and determine whether the resulting imbalance escalates the production of microbial metabolites that increase the risk for cardiovascular disease. Our central hypothesis is that mitochondrial dysfunction induced by an obesogenic HF diet activates epithelial repair responses (e.g., crypt hyperplasia), which in turn drives an expansion of facultative anaerobic Enterobacteriaceae, a taxon known to produce metabolites that accelerate atherosclerosis. To test our hypothesis, we will determine whether mitochondrial dysfunction-induced monocyte recruitment promotes colonic epithelium repair responses (specific aim 1). We will identify the role of colonic epithelium repair responses in driving HF diet-induced Enterobacteriaceae expansion (specific aim 2). We will also elucidate the mechanism by which HF diet-induced Enterobacteriaceae expansion increases circulating trimethylamine N-oxide (TMAO) levels and promotes cardiovascular disease (specific aim 3). By defining the complex order of events that links these disease manifestations, we expect the completion of the proposed experiments to usher in a decisive conceptual advance to understand how HF diet increases cardiovascular disease risk.
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Mariana Xavier Byndloss其他文献

Mariana Xavier Byndloss的其他文献

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{{ truncateString('Mariana Xavier Byndloss', 18)}}的其他基金

Obesogenic diet-induced intestinal epithelium repair responses link dysbiosis and cardiovascular disease
肥胖饮食诱导的肠上皮修复反应将生态失调与心血管疾病联系起来
  • 批准号:
    10345474
  • 财政年份:
    2022
  • 资助金额:
    $ 50.55万
  • 项目类别:
Mechanisms of Salmonella-mediated disruption of colonization resistance in the inflamed gut
沙门氏菌介导的炎症肠道定植抵抗破坏机制
  • 批准号:
    10595200
  • 财政年份:
    2022
  • 资助金额:
    $ 50.55万
  • 项目类别:
Mechanisms of Salmonella-mediated disruption of colonization resistance in the inflamed gut
沙门氏菌介导的炎症肠道定植抵抗破坏机制
  • 批准号:
    10707174
  • 财政年份:
    2022
  • 资助金额:
    $ 50.55万
  • 项目类别:

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