The effect of Diyu on gut microbiota in rats with acute ulcerative colitis
Ulcerative colitis (UC) is a non-specific inflammatory bowel disease (IBD) accompanied by immune abnormalities. The disease has a long course and is prone to recurrence, mainly manifested as diarrhea, abdominal pain, bleeding and other symptoms caused by chronic colonic inflammation. It not only affects the quality of life of patients, but also increases the risk of colon cancer due to long-term recurrent mucosal damage. In recent years, the incidence rate of UC has increased year by year and has become a global disease that affects people’s life and health. Although the pathogenesis of UC is not yet fully understood, it is widely believed to be a comprehensive disease response caused by multiple factors such as environment, genetics, immunity, infection, etc. The gut microbiota, as the main component of the internal environment of the intestine, plays an important regulatory role in various physiological and pathological processes such as intestinal metabolism, immunity, and inflammation. Research has found that changes in the structure of gut microbiota are closely related to the disease progression of UC. Patients with UC have disrupted and imbalanced gut microbiota, while transplantation of normal microbiota can significantly alleviate colitis symptoms, indicating that gut microbiota plays an important regulatory role in the onset and treatment of UC.

Sanguisorba officinalis L. is a perennial herbaceous plant in the Rosaceae family, belonging to the genus Sanguisorba. It is used as a root herb and has the effects of stopping bleeding, cooling blood, detoxifying and astringing sores. It can be used for the treatment of rectal bleeding, hemorrhoids, dysentery, collapse, water fire burns, and abscesses and sores. In recent years, Diyu and its compound preparations, such as Diyu Sanbai Tang, Bing, and Diyu Tang, have shown good clinical treatment effects for UC. However, due to the complex pathogenesis of UC, the mechanism of Diyu in treating UC is still unclear and needs further research.

Therefore, considering the important role of gut microbiota in the pathogenesis of ulcerative colitis, this study intends to use a dextran sulfate sodium (DSS) – induced acute colitis model in rats, and explore the changes in gut microbiota during the treatment of UC with Eucommia ulmoides through high-throughput sequencing technology, in order to elucidate the mechanism of action of Eucommia ulmoides in treating UC intestinal inflammation from a microecological perspective and provide data support and methodological reference for the development of UC related therapeutic drugs.

Ulcerative colitis is a complex inflammatory disease with long-lasting and recurrent symptoms that require long-term effective drug treatment. After thousands of years of clinical application, traditional Chinese medicine has the characteristics of safety, effectiveness, and minimal toxic side effects, and has unique advantages in the treatment of chronic diseases such as UC. The traditional Chinese medicine Diyu belongs to the colon meridian and has the effects of stopping bleeding, cooling blood, clearing heat and detoxifying, converging and stopping diarrhea, demonstrating its potential therapeutic effect on ulcerative colitis.

This study used 3.5% DSS free drinking for 7 days to induce an acute UC model in rats, and explored the improvement effect of Diyu on intestinal inflammation in UC rats from the aspects of body mass, DAI score, tissue morphology, and inflammatory factor levels. The results showed that Diyu can significantly improve the body mass of UC rats, reduce DAI disease scores, improve intestinal epithelial mucosal damage, restore intestinal glandular morphology and tight junctions. IL-6, IL-1 β, and TNF – α are common pro-inflammatory factors, and their levels are closely related to the disease progression of UC. Therefore, this study detected the levels of IL-6, IL-1 β, and TNF – α in the serum and colon tissues of rats. The results showed that the levels of IL-6, IL-1 β, and TNF – α in the serum and colon tissues of the model group rats were significantly increased, and their levels were significantly decreased after intervention with Diyu. The above research results indicate that Diyu has a certain therapeutic effect on DSS induced UC in rats and can improve intestinal inflammation in UC.

Numerous studies have shown a correlation between the structure of gut microbiota and the progression of UC disease. In a sterile environment, DSS or TNBS induced UC symptoms in mice were significantly lower than those in a bacterial environment. In addition, the abundance and diversity of gut microbiota in UC patients decrease, with a decrease in the proportion of Firmicutes and other microbiota, and an increase in the proportion of Proteobacteria and Escherichia coli. The gut of UC patients loses the dynamic stability of the core microbiota. Further microbiota transplantation was performed on UC patients, and it was found that the transplantation of normal fecal microbiota significantly alleviated the symptoms of UC, indicating that the structure of gut microbiota plays an important regulatory role in the pathogenesis and treatment of UC. Traditional Chinese medicine is mostly decocted and taken orally, which inevitably involves contact with the gut microbiota. However, it is currently unclear whether Diyu exerts its therapeutic effect on UC by regulating the gut microbiota. Therefore, this study used high-throughput sequencing technology to analyze the changes in gut microbiota composition of UC rats under the intervention of Eucommia ulmoides, aiming to further explore the intestinal mechanism of Eucommia ulmoides in treating UC through its effect on gut microbiota composition. Research has shown that the intestinal microbiota of the model group rats is disrupted and the diversity of the microbiota is reduced compared to the normal group rats. After intervention with Diyu, the structure of the intestinal microbiota is restored to a certain extent, and the diversity of the intestinal microbiota is also significantly improved. Compared with the model group, Diyu can significantly upregulate the relative abundance of Prevotellaceae UCG-001 and Bifidobacterium (P<0.05, P<0.01), and significantly reduce the relative abundance of Proteobacteria, Bacteroides, and Desulfovibrio (P<0.05, P<0.01). Further correlation analysis revealed that the relative abundance of Proteobacteria, Bacteroides, Desulfovibrio, and Oscillibacter was positively correlated with the levels of IL-6, IL-1 β, and TNF – α in the colon. Among them, Proteobacteria is one of the main phyla that produces endotoxins, and an increase in its relative abundance can easily cause an increase in intestinal toxins, leading to inflammation. Bacteroides, Desulfovibrio, and Oscillibacter are all believed to be closely associated with UC intestinal inflammation and can damage the function of intestinal epithelial mucosa. The relative abundance of Prevotellaceae UCG-001 and Bifidobacterium is negatively correlated with the levels of IL-6, IL-1 β, and TNF – α in the colon, which is consistent with previous studies. The increase in the relative abundance of Prevotellaceae UCG-001 and Bifidobacterium will be beneficial for protecting the intestinal mucosal barrier function and reducing inflammatory reactions. After treatment with Diyu, the relative abundance of the above microbiota decreased towards the normal group, indicating that Diyu can regulate the intestinal microbiota structure of UC rats, accelerate microbiota recovery, and alleviate intestinal inflammation symptoms in UC rats.

In summary, Diyu may treat acute UC by improving the composition of gut microbiota in UC rats, restoring microbiota diversity, repairing mucosal barriers. This study provides a preliminary exploration of the intestinal mechanism by which Eucommia ulmoides improves UC, which can provide some data reference for the clinical application and drug development of Eucommia ulmoides in the treatment of UC.