Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv 62431, Israel.
Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel; 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mol Cell. 2020 May 21;78(4):597-613. doi: 10.1016/j.molcel.2020.03.001. Epub 2020 Mar 23.
Commensal microbial communities inhabit biological niches in the mammalian host, where they impact the host's physiology through induction of "colonization resistance" against infections by a multitude of molecular mechanisms. These colonization-regulating activities involve microbe-microbe and microbe-host interactions, which induce, through utilization of complex bacterial networks, competition over nutrients, inhibition by antimicrobial peptides, stimulation of the host immune system, and promotion of mucus and intestinal epithelial barrier integrity. Distinct virulent pathogens overcome this colonization resistance and host immunity as part of a hostile takeover of the host niche, leading to clinically overt infection. The following review provides a mechanistic overview of the role of commensal microbes in modulating colonization resistance and pathogenic infections and means by which infectious agents may overcome such inhibition. Last, we outline evidence, unknowns, and challenges in developing strategies to harness this knowledge to treat infections by microbiota transfer, phage therapy, or supplementation by rationally defined bacterial consortia.
共生微生物群落栖息在哺乳动物宿主的生物小生境中,通过多种分子机制诱导“定植抗性”,从而影响宿主的生理机能。这些调节定植的活动涉及微生物-微生物和微生物-宿主的相互作用,通过利用复杂的细菌网络,诱导对营养物质的竞争、抗菌肽的抑制、宿主免疫系统的刺激以及促进黏液和肠上皮屏障的完整性。不同的毒力病原体克服这种定植抗性和宿主免疫,作为宿主小生境被接管的一部分,导致临床上明显的感染。以下综述提供了共生微生物在调节定植抗性和致病性感染中的作用的机制概述,以及传染性病原体可能克服这种抑制的方式。最后,我们概述了利用这种知识通过菌群转移、噬菌体治疗或通过合理定义的细菌联合体进行补充来治疗感染的策略方面的证据、未知和挑战。