College of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Microbiol Spectr. 2024 Oct 3;12(10):e0043624. doi: 10.1128/spectrum.00436-24. Epub 2024 Aug 20.
The intact immune system of mice exhibits resistance to colonization by exogenous microorganisms, but the gut microbiota profiles of the humanized mice and the patterns of human fecal microbiota colonization remain unexplored. Humanized NCG (huNCG) mice were constructed by injected CD34 +stem cells. 16S rRNA sequencing and fecal microbiota transplantation (FMT) technologies were used to detect the differences in microbiota and selective colonization ability for exogenous community colonization among three mice cohorts (C57BL/6J, NCG, and huNCG). Flow cytometry analysis showed that all huNCG mice had over 25% hCD45 +in peripheral blood. 16S rRNA gene sequence analysis showed that compared with NCG mice, the gut microbiota of huNCG mice were significantly altered. After FMT, the principal coordinates analysis (PCoA) showed that the gut microbial composition of huNCG mice (huNCG-D9) was similar to that of donors. The relative abundance of Firmicutes and Bacteroidetes were significantly increased in huNCG mice compared to NCG mice. Further comparison of ASV sequences revealed that , , , , and exhibited higher abundance and stability in huNCG mice after FMT. Furthermore, PICRUSt2 analysis showed that huNCG mice had significantly enhanced metabolism and immunity. This study demonstrated that humanized mice are more conducive to colonization within the human gut microbiota, which provides a good method for studying the association between human diseases and microbiota.IMPORTANCEThe gut microbiota and biomarkers of humanized mice are systematically revealed for the first time. The finding that human fecal microbiota colonize humanized mice more stably provides new insights into the study of interactions between immune responses and gut microbiota.
完整的免疫系统使小鼠能够抵抗外源性微生物的定植，但人类化小鼠的肠道微生物组谱和人类粪便微生物定植模式仍未得到探索。通过注射 CD34 +干细胞构建了人类化 NCG（huNCG）小鼠。使用 16S rRNA 测序和粪便微生物群移植（FMT）技术来检测三批小鼠（C57BL/6J、NCG 和 huNCG）之间微生物群的差异和对外源群落定植的选择性定植能力。流式细胞术分析显示所有 huNCG 小鼠的外周血中均有超过 25%的 hCD45 +。16S rRNA 基因序列分析表明，与 NCG 小鼠相比，huNCG 小鼠的肠道微生物群发生了明显变化。FMT 后，主坐标分析（PCoA）表明 huNCG 小鼠（huNCG-D9）的肠道微生物组成与供体相似。与 NCG 小鼠相比，huNCG 小鼠的厚壁菌门和拟杆菌门的相对丰度显著增加。进一步比较 ASV 序列显示， 、 、 、 和 在 FMT 后在 huNCG 小鼠中的丰度和稳定性更高。此外，PICRUSt2 分析表明，huNCG 小鼠的代谢和免疫功能显著增强。本研究表明，人类化小鼠更有利于定植于人类肠道微生物群，为研究人类疾病与微生物群之间的关系提供了良好的方法。
重要的是，首次系统地揭示了人类化小鼠的肠道微生物组和生物标志物。发现人类粪便微生物群更稳定地定植于人类化小鼠，为研究免疫反应和肠道微生物群之间的相互作用提供了新的见解。
