SBIR Phase I: An omics-based computational platform for the personalization of gut microbiome therapeutics

考虑到肠道微生物群现在已知是从哮喘到炎症性肠病等一系列疾病的主要角色之一，这一小企业创新研究(SBIR)第一阶段项目的更广泛的影响/商业潜力是巨大的。这些疾病影响了超过1.2亿人，在美国造成了超过5800亿美元的损失。其中许多疾病的标准治疗方法具有不同的疗效和严重的副作用，需要新的治疗方法。虽然微生物组疗法(MBT)已被证明是一种新的治疗方法，但其疗效在很大程度上受到个体之间高度可变的肠道微生物区系组成的影响。由于在给药前没有可靠的方法来个性化MBTS，MBTS被开发为一种一刀切的治疗方法。因此，主要需要开发具有成本效益的MBTS个性化技术。通过支持新的治疗方案并降低与MBT治疗相关的风险，我们的技术将有助于降低治疗成本和这些疾病在世界范围内的整体经济负担。这个小企业创新研究第一阶段项目通过开发第一项技术，在MBT给药前高效而可靠地个性化，满足了微生物组研究和精确医学交叉的基本需求。越来越多的研究正在发现一系列疾病与肠道微生物群之间的密切联系。因此，MBTS正在成为一种新的医学范式，通过调节肠道微生物区系来对抗各种疾病。然而，一个主要的挑战是肠道微生物群在个体之间的高度可变的组成和功能格局。尽管在过去的几年里对肠道微生物组药物进行了广泛的研究，但由于许多障碍，可靠和强大的技术被证明是难以捉摸的。MBTS个性化的最大挑战是在个体特定的组学数据和MBT-肠道相互作用之间缺乏机制或统计联系。使用机器学习技术和先进的优化方法，我们将开发一个计算平台，作为一个虚拟的、具有成本效益的工具来个性化MBT。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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 Small Business Innovation Research (SBIR) Phase I project is substantial, considering the fact that gut microbiome is now known to be one of the primary role-players in a range of diseases from asthma to inflammatory bowel disease. These diseases affect more than 120 million people and cost more than $580 B in the US. Standard treatments for many of these diseases have variable efficacy and serious side effects, calling for novel therapeutic approaches. While microbiome therapies (MBTs) have proven useful as a new class of therapeutics, their efficacy is largely affected by highly variable gut microbiota composition between individuals. Since there is no reliable approach to personalize MBTs prior to administration, MBTs are developed as a one-size-fits-all treatment. As a result, a major need exists for the development of cost-effective techniques for personalization of MBTs. By enabling new treatment scenarios and mitigating the risks associated with MBT treatments, our technology will help reduce the cost of treatment and the overall economic burden of these diseases worldwide.This Small Business Innovation Research Phase I project addresses an essential need at the intersection of microbiome research and precision medicine by developing the first technology to efficiently and reliably personalize MBTs prior to their administration. A growing body of research is unearthing the close associations between a range of diseases and the gut microbiome. As a result, MBTs are emerging as a new paradigm in medicine to fight various diseases by modulating the gut microbiota. A primary challenge, however, is the highly variable compositional and functional landscape of the gut microbiome across individuals. Despite extensive research on gut microbiome medicine over that past several years, a reliable and robust technology has proven elusive due to many impediments. The biggest challenge in personalization of MBTs is the lack of a mechanistic or statistical link between individual-specific omics data and MBT-gut interactions. Using machine learning techniques and advanced optimization approaches, we will develop a computational platform as a virtual, cost-effective tool to personalize MBTs.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.