Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Microbiome & Cancer Division, DKFZ, Heidelberg, Germany.
Clin Microbiol Infect. 2023 Jun;29(6):682-688. doi: 10.1016/j.cmi.2022.08.027. Epub 2022 Oct 1.
BACKGROUND: Inflammatory bowel disease (IBD) constitutes a group of auto-inflammatory disorders that impact the gastrointestinal tract and other systemic organs. The gut microbiome contributes to IBD pathology through multiple mechanisms. Bacteriophages (hereafter termed phages) are viruses that are able to specifically infect bacteria. Considered as part of the gut microbiome, phages may impact the bacterial community structure in various clinical contexts. Additionally, exogenous phage administration may represent a means of suppressing IBD-associated pathobionts; however, the utilization of phage therapy remains at an early developmental phase. OBJECTIVES: Herein, we summarize the latest advances in understanding endogenous phage impacts on the gut microbiome in a healthy gut and in IBD. We highlight the prospect of phage utilization as a targeted mode of pathobiont eradication, for preventing and treating IBD manifestations and complications. SOURCES: Selected peer-reviewed publications regarding the role of phages in a healthy gut and in IBD, published between 2013 and 2022. CONTENT: The human gut microbiome is increasingly suggested to play a significant role in the onset and progression of multiple non-communicable diseases such as IBD. Several studies suggest that this effect may be mediated by discrete disease-contributing commensals. However, the eradication of such pathogenic bacteria remains a daunting unmet task. Altered community structure in IBD may be influenced by blooms of phages within the gut bacterial ecosystem. Moreover, combinations of phages specifically targeting disease-contributing pathobiont strain clades may be harnessed as potential eradication treatment preventing and treating IBD, while bearing minimal adverse impacts on the surrounding bacterial microbiome. IMPLICATIONS: Understanding the endogenous phage-gut commensal interactions in a healthy gut and in IBD may enable phage utilization in precision gut microbiome editing, towards treating IBD and other non-communicable microbiome-associated diseases. Nevertheless, developing phage combination-mediated IBD pathobiont eradication treatment modalities will likely necessitate better strain-level bacterial target identification and resolution of treatment-related challenges, such as phage delivery, off-target effects, and bacterial resistance.
背景:炎症性肠病(IBD)是一组影响胃肠道和其他全身器官的自身炎症性疾病。肠道微生物组通过多种机制导致 IBD 发病。噬菌体(以下简称噬菌体)是能够专门感染细菌的病毒。作为肠道微生物组的一部分,噬菌体可能会在各种临床情况下影响细菌群落结构。此外,外源性噬菌体给药可能代表一种抑制与 IBD 相关的条件致病菌的方法;然而,噬菌体治疗的利用仍处于早期发展阶段。
目的:本文总结了目前对健康肠道和 IBD 中内源性噬菌体对肠道微生物组影响的最新认识。我们强调了噬菌体作为一种有针对性的根除条件致病菌的方法的应用前景,用于预防和治疗 IBD 表现和并发症。
资料来源:选择了 2013 年至 2022 年间发表的关于噬菌体在健康肠道和 IBD 中作用的同行评议出版物。
内容:人类肠道微生物组被越来越多地认为在多种非传染性疾病(如 IBD)的发病和进展中发挥重要作用。一些研究表明,这种影响可能是由离散的疾病相关共生菌介导的。然而,根除这些致病菌仍然是一个艰巨的未满足的任务。IBD 中群落结构的改变可能受到肠道细菌生态系统中噬菌体数量增加的影响。此外,针对特定疾病相关条件致病菌菌株谱系的噬菌体组合可能被利用为预防和治疗 IBD 的潜在根除治疗方法,同时对周围细菌微生物组的不良影响最小。
意义:了解健康肠道和 IBD 中内源性噬菌体-肠道共生菌相互作用可能使噬菌体在精确的肠道微生物组编辑中得到利用,从而治疗 IBD 和其他非传染性微生物组相关疾病。然而,开发噬菌体组合介导的 IBD 条件致病菌根除治疗方法可能需要更好地确定细菌靶标,并解决与治疗相关的挑战,如噬菌体传递、脱靶效应和细菌耐药性。
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