Curcumin Combined with Tryptophan Ameliorates DSS-Induced Ulcerative Colitis via Reducing Inflammation and Oxidative Stress and Regulation of Gut Microbiota

<b>Background</b>: Curcumin (Cur) and tryptophan (Trp) both show promise for treating ulcerative colitis (UC) alone, but their combination has not been explored. This study investigated the therapeutic advantage of the combination (Cur-Trp) for DSS-induced ulcerative colitis in mice. <b>Methods</b>: We established a mouse model of ulcerative colitis induced by dextran sulfate sodium (DSS). The mice were treated with Cur, Trp, or Cur-Trp, and to evaluate the therapeutic effects, we assessed clinical signs such as body weight, disease activity index (DAI), and colon length. We also examined intestinal barrier function through indicators including histopathological changes, inflammatory factors, oxidative stress levels, mucin secretion, and tight junction protein expression. Additionally, we analyzed the composition of gut microbiota and the content of its metabolites like short-chain fatty acids (SCFAs). <b>Results</b>: The Cur-Trp group produced the most significant improvement, exceeding that of Cur or Trp group. This was evidenced by a significant recovery of this sign, including slower weight loss, reduced colon shortening, and de-creased disease activity index. Compared with the model group, the weight loss of mice in the Cur-Trp group was reduced from 17.15% to 9.73%, which was better than that in the cur group (11.33%) and the Trp group (11.59%). The DAI decreased from the model group (3.6) to the Cur-Trp group (2.4), while the DAI in the Cur group and the Trp group only decreased to 2.9 and 2.8, respectively. The colon length in the Cur-Trp group (6.52 cm) was larger than that in the cur group (6.31 cm), the Trp group (6.23 cm) and the model group (5.5 cm). The Cur-Trp intervention effectively restored intestinal barrier function, as shown by reducing colon tissue dam-age, modulating inflammatory factors, restoring oxidative balance, increasing mucin secretion, and upregulating tight junction protein expression. Further studies showed that the combination uniquely modulated the gut microbiome, increased the Firmicutes/Bacteroidetes (F/B) ratio, decreased the genus of pro-inflammatory bacteria, and in-creased beneficial bacteria, while increasing SCFA levels to alleviate DSS-induced ulcerative colitis. <b>Conclusions</b>: Cur-Trp has shown great potential in alleviating colitis and promoting intestinal barrier function, suggesting that the combination of Cur and Trp has the potential to be developed as a therapeutic functional food or dietary supplement for UC. However, more studies are needed to validate this finding. Future research should focus on elucidating the precise molecular mechanisms, optimizing dosage and clinical trials in chronic models and humans to provide more targeted treatment options.