Impact of dysbiosis on the development of age-related inflammation

生态失调对年龄相关炎症发展的影响

基本信息

  • 批准号:
    10331167
  • 负责人:
  • 金额:
    $ 7.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-30 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Project summary The resident gut microbiota and the host immune system have co-evolved for millennia. However, modern societal conditions have disturbed this co-evolution, coinciding with a steep rise in immune-mediated diseases. Bacterial translocation across the intestinal barrier and into extraintestinal organs such as the visceral adipose tissues can have major pathological consequences. We recently discovered that aging is associated with formation of tertiary lymphoid structures, known as Fat-associated lymphoid clusters (FALCs), in the visceral adipose tissue. As an individual ages, the abundance of anti-inflammatory gut bacteria decreases with a parallel increase in opportunistic pathogens, ultimately leading to disruption of intestinal immunity and barrier function. In two recent studies, the gut commensal species Enterococcus gallinarum was found to have high translocation efficacy, with the ability to translocate to the liver and induce autoimmunity in genetically predisposed mice. In our preliminary experiments, we found that two different strains of E. gallinarum exhibit distinct capacities for translocation, and that rates of translocation for a single E. gallinarum strain vary dramatically between mice mono-colonized with E. gallinarum versus mice colonized with E. gallinarum in the presence of a complex gut microbial community. We hypothesize that translocation of gut microbes to visceral adipose tissue results in FALC formation and age-related inflammation leading to metabolic dysfunction. In this application, we propose to: 1) determine the effect of E. gallinarum translocation and persistence on aging-associated FALC formation and inflammation, and 2) elucidate the mechanism(s) that enable E. gallinarum to translocate and induce aging- associated FALC formation and inflammation. These studies will provide insight into the fundamental mechanisms by which commensal bacteria translocate across the intestinal barrier and induce age-related inflammation. Thus, they may illuminate potential targets for novel therapeutic strategies delay chronic aging with age.
项目总结

项目成果

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VISHWA DEEP DIXIT其他文献

VISHWA DEEP DIXIT的其他文献

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{{ truncateString('VISHWA DEEP DIXIT', 18)}}的其他基金

Caloric restriction-driven immunometabolic checkpoints of inflammation
热量限制驱动的炎症免疫代谢检查点
  • 批准号:
    10457565
  • 财政年份:
    2022
  • 资助金额:
    $ 7.06万
  • 项目类别:
Yale Murine-TMC on Immune Cell Senescence Derived Inflammation
耶鲁小鼠-TMC 对免疫细胞衰老引起的炎症的研究
  • 批准号:
    10675111
  • 财政年份:
    2022
  • 资助金额:
    $ 7.06万
  • 项目类别:
Caloric restriction-driven immunometabolic checkpoints of inflammation
热量限制驱动的炎症免疫代谢检查点
  • 批准号:
    10656332
  • 财政年份:
    2022
  • 资助金额:
    $ 7.06万
  • 项目类别:
Immunometabolic regulation of bone inflammaging
骨炎症的免疫代谢调节
  • 批准号:
    10430514
  • 财政年份:
    2022
  • 资助金额:
    $ 7.06万
  • 项目类别:
Immunometabolic regulation of bone inflammaging
骨炎症的免疫代谢调节
  • 批准号:
    10641819
  • 财政年份:
    2022
  • 资助金额:
    $ 7.06万
  • 项目类别:
Yale Murine-TMC on Immune Cell Senescence Derived Inflammation
耶鲁小鼠-TMC 对免疫细胞衰老引起的炎症的研究
  • 批准号:
    10553032
  • 财政年份:
    2022
  • 资助金额:
    $ 7.06万
  • 项目类别:
Impact of dysbiosis on the development of age-related inflammation
生态失调对年龄相关炎症发展的影响
  • 批准号:
    10396668
  • 财政年份:
    2020
  • 资助金额:
    $ 7.06万
  • 项目类别:
Impact of dysbiosis on the development of age-related inflammation
生态失调对年龄相关炎症发展的影响
  • 批准号:
    10667392
  • 财政年份:
    2020
  • 资助金额:
    $ 7.06万
  • 项目类别:
Impact of dysbiosis on the development of age-related inflammation
生态失调对年龄相关炎症发展的影响
  • 批准号:
    10259710
  • 财政年份:
    2020
  • 资助金额:
    $ 7.06万
  • 项目类别:
Impact of Ketone Metabolites on Inflammasome Deactivation in Gout
酮代谢物对痛风炎症小体失活的影响
  • 批准号:
    10091969
  • 财政年份:
    2017
  • 资助金额:
    $ 7.06万
  • 项目类别:

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