and HKL Suspension Alleviates Ulcerative Colitis in Rats by Regulating Gut Microbiota, Suppressing TLR9, and Promoting Metabolism.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with complex pathogenesis. The intestinal flora disturbance affects the homeostasis of the intestinal environment, leading to metabolic imbalance and immune abnormalities of the host, contributing to the perpetuation of intestinal inflammation. We suggest that the combination of anti-inflammatory therapy and the regulation of intestinal flora balance may help in the treatment process. Previously, we used a combination treatment consisting of (Lac) and Chinese medicine Huan Kui Le (HKL) suspension in a UC rat model, where the combined intervention was more effective than either treatment alone. Herein, the mechanism of action of this combined treatment has been investigated using 16S rRNA sequencing, immunohistochemistry, and ELISA methods in the colon, and untargeted metabolomics profiling in serum. Colon protein expression levels of IL-13 and TGF-β were upregulated, whereas those of TLR9 and TLR4 were downregulated, consistent with an anti-inflammatory effect. In addition, gut microbiota structure changed, shown by a decrease in opportunistic pathogens correlated with intestinal inflammation, such as and , and an increase in beneficial bacteria such as . The latter correlated positively with IL-13 and TGF-β and negatively with IFN-γ. Finally, this treatment alleviated the disruption of the metabolic profile observed in UC rats by increasing short-chain fatty acid (SCFA)-producing bacteria in the colonic epithelium. This combination treatment also affected the metabolism of lactic acid, creatine, and glycine and inhibited the growth of . Overall, we suggest that treatment combining probiotics and traditional Chinese medicine is a novel strategy beneficial in UC that acts by modulating gut microbiota and its metabolites, TLR9, and cytokines in different pathways.