B-10: Biosecurity and Public Health Group, Bioscience Division, Los Alamos National Laboratorygrid.148313.c, Los Alamos, New Mexico, USA.
Infect Immun. 2022 May 19;90(5):e0058921. doi: 10.1128/iai.00589-21. Epub 2022 Apr 6.
Humans are considered "superorganisms," harboring a diverse microbial collective that outnumbers human cells 10 to 1. Complex and gravely understudied host- and microbe-microbe interactions-the product of millions of years of host-microbe coevolution-govern the superorganism in almost every aspect of life functions and overall well-being. Abruptly disrupting these interactions via extrinsic factors has undesirable consequences for the host. On the other hand, supplementing commensal or beneficial microbes may mitigate perturbed interactions or enhance the interactive relationships that ultimately benefit all parties. Hence, immense efforts have focused on dissecting the innumerable host- and microbe-microbe relationships to characterize if a "positive" or "negative" interaction is at play and to exploit such behavior for broader implications. For example, microbiome research has worked to identify and isolate naturally antipathogenic microbes that may offer therapeutic potential either in a direct, one-on-one application or by leveraging its unique metabolic properties. However, the discovery and isolation of such desired therapeutic microbes from complex microbiota have proven challenging. Currently, there is no conventional technique to universally and functionally screen for these microbes. With this said, we first describe in this review the historical (probiotics) and current (fecal microbiota or defined consortia) perspectives on therapeutic microbes, present the discoveries of therapeutic microbes through exploiting microbe-microbe and host-microbe interactions, and detail our team's efforts in discovering therapeutic microbes via our novel microbiome screening platform. We conclude this minireview by briefly discussing challenges and possible solutions with therapeutic microbes' applications and paths ahead for discovery.
人类被认为是“超级生物体”，体内寄居着大量的微生物群体，其数量是人体细胞的 10 倍到 1 倍。复杂且严重研究不足的宿主-微生物相互作用和微生物-微生物相互作用是宿主与微生物数百万年共同进化的产物，几乎控制着超级生物体生命功能和整体健康的各个方面。通过外部因素突然干扰这些相互作用会对宿主产生不良后果。另一方面，补充共生或有益的微生物可以减轻失调的相互作用或增强最终使所有各方受益的相互关系。因此，人们付出了巨大的努力来剖析无数的宿主-微生物和微生物-微生物相互关系，以确定是否存在“积极”或“消极”的相互作用，并利用这种行为产生更广泛的影响。例如，微生物组研究致力于识别和分离天然抗病原体微生物，这些微生物可能具有治疗潜力，无论是在直接的一对一应用中，还是利用其独特的代谢特性。然而，从复杂的微生物群中发现和分离出这些理想的治疗性微生物一直具有挑战性。目前，没有常规技术可以普遍而有效地筛选这些微生物。话虽如此，我们首先在这篇综述中描述了治疗性微生物的历史（益生菌）和当前（粪便微生物群或定义的联合体）观点，介绍了通过利用微生物-微生物和宿主-微生物相互作用来发现治疗性微生物的发现，并详细介绍了我们团队通过我们新颖的微生物组筛选平台发现治疗性微生物的努力。最后，我们简要讨论了治疗性微生物应用的挑战和可能的解决方案，以及发现的未来方向。
