Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan.
Nature. 2019 Jan;565(7741):600-605. doi: 10.1038/s41586-019-0878-z. Epub 2019 Jan 23.
There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103 dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
人们越来越意识到肠道微生物群作为各种疾病治疗靶点的重要性。然而，目前只有少数已知的共生菌株可能被用于操纵宿主的生理功能。在这里，我们从健康的人类供体粪便中分离出一组由 11 个细菌菌株组成的混合物，该混合物能够在肠道中强烈诱导产生干扰素-γ的 CD8 T 细胞。这 11 个菌株共同作用，以不引起炎症的方式介导诱导，这依赖于 CD103 树突状细胞和主要组织相容性（MHC）I 类分子。用 11 种混合菌株对小鼠进行定植，增强了宿主对李斯特菌感染的抵抗力，并增强了同种肿瘤模型中免疫检查点抑制剂的治疗效果。这 11 种菌株主要代表人类微生物组中罕见的、低丰度的成分，因此具有作为广泛有效的生物治疗剂的巨大潜力。
