Gene editing is a precise technique for modifying the genome, providing a powerful tool for investigating gene function. Utilizing methods such as zinc finger nucleases (ZFNs), transcription-activator like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR), researchers can manipulate target genes to knock out, insert, or modify specific genes in mouse models to study their impact on gut microbiome composition. This enables exploration of the mechanisms of gut microbiome/host interactions and understanding the impact of these interactions on host health. Recent studies have revealed significant advances in the effects of gene editing on the gut microbes of mice, where knocking out specific genes can lead to changes in microbial composition that affect host metabolism, immunity, and disease risk. These studies unveil a complex network of interactions between gut microbes and their hosts, providing important insights into key factors in gut microbiology and host health. In the future, further research into the effects of mouse genome editing on gut microbes will help develop new therapeutic strategies and preventive measures to maintain host health.