The intestinal microbiota is a complex ecosystem that plays an important role in promoting food digestion, xenobiotic metabolism, and regulating innate and adaptive immune processes (Belizário and Faintuch, 2018). Research shows that factors such as diet, age, stress, and disease can lead to a reduction in the relative abundance and diversity of gut microbial populations, a loss of beneficial microbiota, or an overgrowth of harmful microbiota. This persistent imbalance of microbial communities is called dysbiosis or intestinal flora imbalance (Hrncir, 2022). It is worth noting that dysbiosis is closely related to the pathogenesis of a variety of intestinal and extraintestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), obesity, diabetes, heart disease and vascular diseases, etc. (Meng et al., 2020; Fan and Pedersen, 2021). For current research, it appears that a significant portion of environmental impacts on human health and disease risk is mediated or altered by microbial communities (Fan and Pedersen, 2021; Lynch and Pedersen, 2016). Therefore, the regulation of dysbiosis is particularly important. The mainstream treatment options for dysbiosis mainly include oral probiotics and Fecal Microbiota Transplantation (FMT). However, problems such as inconvenient storage of probiotics and insufficient sources of fecal donors still require us to further explore new treatment options.

Traditional Chinese Medicine (TCM) exerts unique advantages in treating dysbiosis. It is characterized by minimizing drug side effects, reducing the possibility of recurrence, and reducing economic burden (Yao et al., 2024). But similarly, the multi-component and multi-target characteristics of TCM also bring challenges to determining its exact mechanism of action. Dahuang Huanglian Xiexin decoction (XXD), derived from Zhang Zhongjing's Treatise on Typhoid Fever, has been used to treat digestive system diseases for nearly two thousand years (Tong et al., 2023). It is mainly composed of three natural medicines, including Dahuang (Rheum palmatum L.), Huanglian (Coptis chinensis Franch.), and Huangqin (Scutellaria baicalensis Georgi). Modern pharmacological research shows that the combination of three drugs exhibits significant anti-inflammatory and immunomodulatory effects (Yan et al., 2023; Han et al., 2013). So far, XXD is still used clinically to treat digestive diseases such as peptic ulcer, atrophic gastritis and bile reflux gastritis (Gong et al., 2014). In recent years, the potential mechanism of XXD improving type 2 diabetes mellitus (T2DM) through the metabolic activity of tract microbiota has been confirmed (Zhang et al., 2021b), and its efficacy on IBD is also commendable (Han et al., 2013). However, the underlying molecular mechanisms by which XXD ameliorates dysbiosis by modulating host gut microbial composition remain largely undefined.

At present, network pharmacology has become an effective tool for identifying potential active ingredients and action targets of TCM. On this basis, it will become more convenient to predict the mechanism of action of TCM (Yao et al., 2024; Xin et al., 2021; Zhao et al., 2023). In early studies, we found that XXD had a better effect on improving dysbiosis model mice. Therefore, in order to further discover the mechanism of XXD regulating dysbiosis, we used network pharmacology to make preliminary predictions and follow-up. The prediction mechanism was verified in the experiment, aiming to lay a solid theoretical foundation for XXD treatment of dysbiosis.