Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
Nat Rev Immunol. 2019 May;19(5):305-323. doi: 10.1038/s41577-019-0144-5.
Trillions of microorganisms transit through and reside in the mammalian gastrointestinal tract each day, collectively producing thousands of small molecules and metabolites with local and systemic effects on host physiology. Identifying effector microorganisms that causally affect host phenotype and deciphering the underlying mechanisms have become foci of microbiome research and have begun to enable the development of microbiota-based therapeutics. Two complementary, reductionist approaches have commonly been used: the first starts with an immune phenotype and narrows down the microbiota to identify responsible effector bacteria, while the second starts with bacteria-derived molecules and metabolites and seeks to understand their effects on the host immune system. Together, these strategies provide the basis for the rational design of microbial and metabolite-based therapeutics that target and ameliorate immune deficits in patients.
每天都有大量微生物在哺乳动物胃肠道中穿行和定植，它们共同产生数千种小分子和代谢物，对宿主生理产生局部和全身影响。确定那些能对宿主表型产生因果影响的效应微生物，并揭示其潜在机制，已成为微生物组研究的重点，并开始使基于微生物组的治疗方法得以发展。目前常用的两种互补的简化方法是：第一种方法从免疫表型开始，缩小微生物组范围，以确定负责的效应细菌；而第二种方法则从细菌衍生的分子和代谢物开始，寻求理解它们对宿主免疫系统的影响。这些策略共同为合理设计靶向和改善患者免疫缺陷的微生物和代谢物治疗方法提供了基础。
