Maor Moshe, Levy Barazany Hilit, Kolodkin-Gal Ilana
Lauder School of Government, Diplomacy & Strategy, Reichman University, Herzliya, Israel.
Scojen Institute for Synthetic Biology, Dina Recanati School of Medicine, Reichman University, Herzliya, Israel.
Gut Microbes. 2025 Dec;17(1):2517377. doi: 10.1080/19490976.2025.2517377. Epub 2025 Jun 12.
The three main types of live bacterial therapies - probiotics, fecal/microbiome transplants, and engineered bacterial therapies - hold immense potential to revolutionize medicine. While offering targeted and personalized treatments for various diseases, these therapies also carry risks such as adverse immune reactions, antibiotic resistance, and the potential for unintended consequences. Therefore, developing and deploying these therapies necessitates a robust regulatory framework to protect public health while fostering innovation. In this paper, we propose a novel conceptual tool - the -which can assist in the design of robust regulatory regimes which encompass medicine practices based not only on definitive Randomized Controlled Trials (RCTs), but also on meta-analyses, observational studies, and clinicians experience. Regulatory stringency refers to the strictness of regulations, while regulatory balance concerns the degree of alignment between the regulatory framework governing a technology and the actual risks posed by specific products within that technology. Focusing on the US regulatory environment, we subsequently position the three types of live bacterial therapies on the . The insight gained from this exercise demonstrates that probiotics are generally positioned at the bottom of the , corresponding to low-stringency regulation, with a proportionate regulatory balance. However, probiotics intended for high-risk populations are currently subject to low-stringency regulations, resulting in under-regulation. Our analysis also supports the conclusion that fecal microbiota transplants (FMT) for recurrent infection should be positioned close to but below the threshold for under regulation by the U.S. Food and Drug Administration (FDA), and we recommend improved donor screening procedures, preservation and processing, storage, and distribution. Our framework can serve as a scale to assess regulatory gaps for live bacterial therapies and to identify potential solutions where such gaps exist.
三种主要的活菌疗法——益生菌、粪便/微生物群移植和工程菌疗法——具有彻底改变医学的巨大潜力。这些疗法在为各种疾病提供针对性和个性化治疗的同时，也存在诸如不良免疫反应、抗生素耐药性以及意外后果的可能性等风险。因此，开发和应用这些疗法需要一个强大的监管框架，以保护公众健康，同时促进创新。在本文中，我们提出了一种新颖的概念工具—— ，它可以协助设计强大的监管制度，这些制度不仅基于确定性随机对照试验（RCT），还基于荟萃分析、观察性研究和临床医生经验来涵盖医学实践。监管严格性指的是法规的严格程度，而监管平衡则涉及管理一项技术的监管框架与该技术内特定产品所带来的实际风险之间的契合度。随后，我们以美国监管环境为重点，将三种活菌疗法置于 之上。从这项分析中获得的见解表明，益生菌通常处于 的底部，对应低严格性监管以及相应的监管平衡。然而，针对高风险人群的益生菌目前受到低严格性监管，导致监管不足。我们的分析还支持这样的结论，即用于复发性 感染的粪便微生物群移植（FMT）应定位在接近但低于美国食品药品监督管理局（FDA）监管不足阈值的位置，并且我们建议改进供体筛查程序、保存和处理、储存及分发。我们的框架可作为一个尺度，用于评估活菌疗法的监管差距，并在存在此类差距的地方识别潜在解决方案。
