摘要Background : 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 fo-cused on gut microbiota fluctuation among representative mouse strains. Methods : 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. Results : 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 2 = 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 signifi-cantly decreased in the IDA, GEA, and DRA groups, whereas those of Saccharimonas , Rikenella , and Odoribacter all significantly increased.