Lynch Lauren E, Lahowetz Rachel, Maresso Christian, Terwilliger Austen, Pizzini Jason, Melendez Hebib Valeria, Britton Robert A, Maresso Anthony W, Preidis Geoffrey A
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
Department of Molecular Virology and Microbiology.
J Clin Invest. 2025 Jun 2;135(11). doi: 10.1172/JCI184323.
A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, ecological, and structural aspects of native communities within the gastrointestinal tract, occupying varying nutritional niches and providing the host with a stable, robust, and diverse gut microbiota that can prevent pathobiont colonization by way of colonization resistance. Alternatively, phage therapy is the use of lytic phage to treat bacterial infections. The rise of antimicrobial resistance has led to renewed interest in phage therapy, and the high specificity of phages for their hosts has spurred interest in using phage-based approaches to precisely modulate the microbiome. In this Review, we consider the present and future of microbiome-targeting therapies, with a special focus on early-life applications, such as prevention of necrotizing enterocolitis.
大量证据表明，单一菌株和多菌株益生菌以及合生元可能在特定胃肠道疾病的管理中发挥作用。然而，目前对临床数据的质量和异质性、易感人群的安全性以及含活微生物产品缺乏监管等问题，阻碍了其在临床上的广泛应用。必须解决安全和监管问题，并考虑新技术。一种未来的替代策略是使用合成细菌群落，即由两种或更多种最初源自人类胃肠道的细菌人工组装而成的联合体。合成细菌群落可以模拟胃肠道内天然群落的功能、生态和结构方面，占据不同的营养生态位，并为宿主提供稳定、强健和多样的肠道微生物群，通过定植抗性防止致病共生菌的定植。或者，噬菌体疗法是使用裂解性噬菌体来治疗细菌感染。抗生素耐药性的增加引发了人们对噬菌体疗法的新兴趣，噬菌体对其宿主的高度特异性激发了人们对使用基于噬菌体的方法精确调节微生物组的兴趣。在这篇综述中，我们考虑了针对微生物组疗法的现状和未来，特别关注早期生命应用，如预防坏死性小肠结肠炎。
