I-Corps: Fenchol Enriched Dietary Supplements

这个I-Corps项目更广泛的影响/商业潜力是开发一种膳食补充剂，可以预防认知障碍和认知能力下降的发生。肠道微生物组在维持健康的认知健康方面发挥着重要作用，然而，微生物组的不利变化可能导致认知能力下降。微生物组有益于大脑和其他健康措施的途径正在通过产生有益的代谢物（如短链脂肪酸）而发挥作用。临床前研究表明，短链脂肪酸如乙酸酯、丙酸酯和丁酸酯可以预防痴呆。然而，长期保持健康有益的微生物组在现实生活中很难实践。 所提出的技术专注于开发一种天然来源的罗勒提取物膳食补充剂，其形式为药用食品，用于维持老年人的健康肠脑轴和认知健康。这个I-Corps项目的基础是开发一种膳食补充剂，促进健康的微生物组，以降低与衰老相关的认知能力下降和痴呆症的风险。该技术是基于模拟微生物组合成短链脂肪酸的作用机制而发现的，这些脂肪酸对维持健康的大脑功能具有有益作用。短链脂肪酸保护神经细胞免受各种细胞毒性暴露，并通过游离脂肪酸受体维持大脑健康。游离脂肪酸受体在神经元中大量表达，因此，它们的作用可以直接调节大脑健康。然而，短链脂肪酸不能通过口服途径到达大脑。为了克服这一缺点，一种与短链脂肪酸具有相似特性的罗勒提取物化合物--小茴香醇（fenchol）被确认为一种激活游离脂肪酸受体、保护大脑健康免受神经退行性疾病影响的方法。该奖项反映了NSF的法定使命，通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of a dietary supplement that may prevent the onset of cognitive disorders and decline. The gut microbiome plays an important role in maintaining healthy cognitive health, however, adverse changes in the microbiome can contribute to cognitive decline. The pathway by which the microbiome benefits the brain and other health measures is showing action through the production of beneficial metabolites such as short chain fatty acids. Preclinical studies have shown that short chain fatty acids like acetate, propionate, and butyrate protect against dementia. However, maintaining a healthy beneficial microbiome over the long-term is hard to practice in real-life. The proposed technology focuses on developing a naturally derived basil extract dietary supplement in the form of a medicinal food for maintaining a health gut-brain axis and cognitive health in elderly individuals. This I-Corps project is based on the development of a dietary supplement that promotes a healthy microbiome to reduce the risk of cognitive decline and dementia associated with aging. The technology was discovered based on mimicking the mechanism of action of microbiome synthesized short chain fatty acids that have beneficial effects in maintaining healthy brain function. Short chain fatty acids protect neuronal cells from various cytotoxic exposures and maintain brain health through free fatty acid receptors. Free fatty acid receptors are abundantly expressed in the neurons, therefore, their actions are amenable to directly modulate brain health. However, short chain fatty acids are not able to reach the brain when given through the oral route. To overcome this drawback, fenchol, a basil extract compound that has similar properties to short chain fatty acids, has been identified as a way to activate the free fatty acid receptors and protect the brain health from neurodegeneration.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.