美国国立卫生研究院Barbara Rehermann小组近日取得一项新成果。经过不懈努力，他们的论文发现了在具有野生衍生微生物群的实验室小鼠群体中，天然免疫反应多年来保持稳定。相关论文于2025年7月28日发表在《免疫学》杂志上。

该研究团队评估了第一个C57BL/6小鼠菌落与自然微生物群（野生小鼠）的长期稳定性和免疫表型。野生小鼠肠道菌群的α-多样性和丰富度在5年内保持了增加，稳定性明显高于实验室小鼠。野生小鼠各器官的骨髓细胞数量增加，自然杀伤细胞、B细胞和T细胞的激活和功能增加，这些细胞可以通过共热转移到实验室小鼠身上。两个临床前模型的免疫读数在整个随访期间保持稳定。这些结果表明，在基础和临床前研究中，维持天然的、野生的微生物群作为共享抗性的小鼠菌落是可行的。

据悉，自由生活的哺乳动物携带着复杂的微生物群，这些微生物群与宿主共同进化了亿万年。这种微生物群从野生小鼠转移到遗传上可驯化的实验室小鼠，已被证明可以在临床前研究中增强人类免疫反应的建模。

附：英文原文

Title: Naturalized immune responses are stable over years in a colony of laboratory mice with wild-derived microbiota

Author: Ji Hoon Oh, Benedikt Hild, Tomoaki Yoshida, Jonathan H. Badger, Jun Seishima, John A. McCulloch, Min Kyung Jung, Shahar Azar, Giorgio Trinchieri, Barbara Rehermann

Issue&Volume: 2025-07-28

Abstract: Free-living mammals carry complex microbiota that co-evolved with their hosts over eons of years. The transfer of such microbiota from wild mice to genetically tractable laboratory mice has been shown to enhance modeling of human immune responses in preclinical studies. Here, we assessed the long-term stability of microbiota and immune phenotype of the first C57BL/6 mouse colony with natural microbiota (wildling mice). The bacterial gut microbiota of wildling mice maintained its increased α-diversity and richness over 5 years, with significantly greater stability than the gut microbiota of laboratory mice. Wildling mice had increased myeloid cell numbers across organs and increased activation and function of natural killer, B, and T cells, which was transferable to laboratory mice via co-housing. Immunological readouts in two preclinical models remained stable throughout the follow-up. These results demonstrate the feasibility of maintaining mouse colonies with natural, wild-derived microbiota as a sharable resource for basic and preclinical research.

DOI: 10.1016/j.immuni.2025.07.004

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00313-9