Clinical trial exploring the diet-microbiome axis in allo-HCT patients

项目总结/摘要-项目4 异基因造血干细胞移植（allo-HCT）是一种有效的细胞治疗形式， 具有治愈恶性和良性血液病的潜力。然而，它的效用是有限的 移植物抗宿主病（GVHD）的发展。GI GVHD是非- allo-HCT后复发死亡率（NRM）。最近的证据使人们注意到， 在GI GVHD的严重程度中，源自宿主与微生物群相互作用的代谢物。但 生物学机制、临床可行性以及改变GI微生物代谢产物对GI GVHD仍然未知。项目4将侧重于微生物代谢组学的饮食操纵 通过饮食补充抗性马铃薯淀粉（RPS）减轻allo-HCT中的GVHD 患者该项目包括一项研究者发起的概念验证临床试验， 项目1和项目3产生的初步数据。这次审判 在FDA的IND下进行。它包括连续的生物样品（粪便和血浆）采集， 微生物群和代谢物改变的分析，由项目1的机制研究提供信息， 2和3。我们还将联合收割机将这些数据与分子的纵向测量结合起来，反映 肠上皮损伤，共同包括发现方法，以更全面地研究 RPS对allo-HCT患者中微生物组、其依赖性代谢物和宿主的影响。

PROJECT SUMMARY/ABSTRACT – PROJECT 4 Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potent form of cellular therapy that has the potential to cure malignant and benign hematological conditions. However, its utility is limited by the development of graft-versus-host disease (GVHD). GI GVHD is the principal cause of non- relapse mortality (NRM) after allo-HCT. Recent evidence has brought into focus the role played by the metabolites derived from host-microbiota interactions in the severity of GI GVHD. However, the biological mechanisms, clinical feasibility, and the impact of altering the GI microbial metabolites on GI GVHD remain unknown. Project 4 will focus on dietary manipulation of the microbiome-metabolomic axis via dietary supplementation with resistant potato starch (RPS) for mitigating GVHD in allo-HCT patients. This project encompasses an investigator initiated proof-of-concept clinical trial that has been developed to translate the preliminary data generated from Projects 1 and 3. This trial is being performed under an IND from the FDA. It includes serial biosample (stool and plasma) collection and analyses for the microbiota and metabolite alterations, informed by mechanistic studies from projects 1, 2, and 3. We will also combine these data with longitudinal measurement of molecules reflecting intestinal epithelial injury, collectively comprising discovery approaches to more comprehensively study the effects of RPS on the microbiome, its dependent metabolites and host in allo-HCT patients.