Objective: The objective of this study is to investigate the differences in the therapeutic effects of recombinant GLP-2 and Lactobacillus plantarum L9, both alone and in combination, for treating UC, providing new directions for future acute UC therapy.

Methods: The GLP-2 homologous peptide from Amphiuma tridactylum species was screened via the NCBI database, and its advanced structure and molecular function were bioinformatically predicted. This fragment was then recombined into the plasmid pET-28a (+) and transformed into Escherichia coli Rosetta (BL21). IPTG induced the expression of the recombinant protein, which was purified, followed by thrombin cleavage to obtain Tuxtide peptides. These peptides were separated via Native PAGE and purified using Trition X-114 and dialysis methods. Acute UC model mice were established using 3% DSS. Changes in body weight and disease activity index scores during the medication period were recorded and analyzed. Colon length and spleen index of mice in each group were measured, and HE staining and colon histology scoring were performed. ELISA was used to detect myeloperoxidase and interleukin-1β in mouse colon tissue.

Results: Compared to the DSS group, the colon length of mice in all treatment groups improved, with significant effects observed in the Tuxtide and Tuxtide+L9 groups (P<0.05). Body weight in all treatment groups rebounded compared to the DSS group, and DAI scores decreased (P<0.05), with the Tuxtide group showing the best improvement in body weight. All treatment groups alleviated intestinal mucosal pathological damage to varying degrees compared to the DSS group, with the Tuxtide+L9 group showing the best anti-inflammatory effect, reducing colon histology scores and restoring intestinal crypts (P<0.1).

Conclusions: Both Tuxtide alone and in combination with Lactobacillus plantarum L9 can alleviate symptoms in mice with acute ulcerative colitis.