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

项目摘要/摘要--项目4 异基因造血干细胞移植(allo-hct)是一种有效的细胞疗法， 具有治愈恶性和良性血液疾病的潜力。然而，它的实用性是有限的。 由于移植物抗宿主病(GVHD)的发展。胃肠道移植物抗宿主病是非 异基因HCT后复发死亡率(NRM)。最近的证据使人们注意到了 GI GVHD严重程度下宿主-微生物区系相互作用产生的代谢物。然而， 胃肠道微生物代谢产物改变的生物学机制、临床可行性及对胃肠道的影响 GVHD仍然未知。项目4将侧重于微生物组-代谢组的饮食操作 通过饮食补充抗性马铃薯淀粉(RPS)缓解allo-HCT中GVHD的Axis 病人。该项目包括研究人员发起的概念验证临床试验，该试验已 为翻译项目1和项目3产生的初步数据而开发。这项试验正在进行中 根据FDA的IND执行。它包括连续的生物样本(粪便和血浆)收集和 微生物区系和代谢物变化的分析，由项目1的机械研究提供信息， 2和3。我们还将把这些数据与分子反射的纵向测量相结合 肠上皮损伤，共同构成更全面研究的发现途径 RPS对allo-HCT患者微生物群及其依赖代谢产物和宿主的影响。

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.