Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Animal Model Exp Med. 2022 Dec;5(4):337-349. doi: 10.1002/ame2.12257. Epub 2022 Jul 26.
Experimental animals are used to study physiological phenomena, pathological mechanisms, and disease prevention. The gut microbiome is known as a potential confounding factor for inconsistent data from preclinical studies. Although many gut microbiome studies have been conducted in recent decades, few have focused on gut microbiota fluctuation among representative mouse strains.
A range of frequently used mouse strains were selected from 34 isolation packages representing disease-related animal (DRA), immunity defect animal (IDA), or gene-editing animal (GEA) from the BALB/c and C57BL/6J backgrounds together with normal mice, and their microbial genomic DNA were isolated from mouse feces to sequence for the exploration of gut microbiota.
Mouse background strain, classification, introduced source, introduced year, and reproduction type significantly affected the gut microbiota structure (p < 0.001 for all parameters), with background strain contributing the greatest influence (R = 0.237). In normal groups, distinct gut microbiota types existed in different mouse strains. Sixty-four core operational taxonomic units were obtained from normal mice, and 12 belonged to Lactobacillus. Interestingly, the gut microbiota in C57BL/6J was more stable than that in BALB/c mice. Furthermore, the gut microbiota in the IDA, GEA, and DRA groups significantly differed from that in normal groups (p < 0.001 for all). Compared with the normal group, there was a significantly higher Chao1 and Shannon index (p < 0.001 for all) in the IDA, GEA, and DRA groups. Markedly changed classes occurred with Firmicutes and Bacteroidetes. The abundances of Helicobacter, Blautia, Enterobacter, Bacillus, Clostridioides, Paenibacillus, and Clostridiales all significantly decreased in the IDA, GEA, and DRA groups, whereas those of Saccharimonas, Rikenella, and Odoribacter all significantly increased.
实验动物被用于研究生理现象、病理机制和疾病预防。肠道微生物组被认为是导致临床前研究数据不一致的潜在混杂因素。尽管近几十年来进行了许多肠道微生物组研究，但很少有研究关注代表性小鼠品系之间的肠道微生物群波动。
从 34 个疾病相关动物（DRA）、免疫缺陷动物（IDA）或基因编辑动物（GEA）的隔离包中选择了一系列常用的小鼠品系，包括 BALB/c 和 C57BL/6J 背景下的正常小鼠，并从其粪便中提取微生物基因组 DNA 进行测序，以探索肠道微生物群。
小鼠背景品系、分类、来源、引入年份和繁殖类型显著影响肠道微生物群结构（所有参数 p<0.001），其中背景品系的影响最大（R=0.237）。在正常组中，不同的小鼠品系存在不同的肠道微生物群类型。从正常小鼠中获得了 64 个核心操作分类单元，其中 12 个属于乳杆菌属。有趣的是，C57BL/6J 小鼠的肠道微生物群比 BALB/c 小鼠更稳定。此外，IDA、GEA 和 DRA 组的肠道微生物群与正常组有显著差异（所有 p<0.001）。与正常组相比，IDA、GEA 和 DRA 组的 Chao1 和 Shannon 指数显著升高（所有 p<0.001）。厚壁菌门和拟杆菌门的显著变化。IDA、GEA 和 DRA 组的 Helicobacter、Blautia、Enterobacter、Bacillus、Clostridioides、Paenibacillus 和 Clostridiales 的丰度显著降低，而 Saccharimonas、Rikenella 和 Odoribacter 的丰度显著增加。
