Objective This study aimed to investigate the impact of sciatic nerve transection on the gut microbiota in mice by establishing a sciatic nerve injury model and analyzing changes using 16S rRNA gene sequencing. Methods Eighteen C57BL / 6 mice were randomly divided into six groups: sham-operated(sham), and experimental groups(postoperative Day 1 (D1), Day 4 (D4), Day 7 (D7), Day 14 (D14), and Day 28 (D28) groups). Colonic contents were collected at different time points after model induction for 16S rRNA sequencing to assess alterations in microbial composition and predict functional changes in the gut microbiome. Results A clear temporal shift in the gut microbial community structure was observed following sciatic nerve transection. From Day 4 post-surgery, microbial richness and diversity showed a significant decline, indicating a disturbance in microbial homeostasis. By Day 7, partial recovery in community richness was noted, suggesting a transient adaptation phase.Taxonomic analysis revealed significant fluctuations in the relative abundance of dominant bacterial phyla, particularly Firmicutes, Verrucomicrobiota, and Proteobacteria. At the genus level, the abundance of Akkermansia progressively declined over time in the experimental groups compared to the sham group, while Kurthia and Dubosiella demonstrated a notable increase starting on Day 4 and peaking on Day 7. These dynamic changes imply specific microbial taxa are responsive to peripheral nerve injury. Furthermore, microbial functional prediction suggested that several metabolic pathways, including lipid and amino acid metabolism, may be affected after sciatic nerve transection in mice. These findings suggest a close association between nerve injury and gut microbial functional attenuation. Conclusions Sciatic nerve transection induced significant alterations in the gut microbiota composition of mice, accompanied by changes in metabolism-related pathways as predicted by functional gene analysis. These findings suggest that the potential functions of gut microbes may be affected. Further validation through metabolomic analysis is required,which may provide valuable insights into the potential role of gut microbiota in peripheral nerve injury repair.