Inflammatory bowel disease (IBD), that includes Crohn's disease (CD) and ulcerative colitis (UC), is an acute intestinal disease characterised by inflammation and damage to the intestinal epithelial barrier (Abraham and Cho, 2009; Chang, 2020). Clinical manifestations such as acute pain, diarrhoea, bloody stools and other symptoms cause great suffering to patients (Tang et al., 2011; Yamabe et al., 2019). Although the pathogenesis of IBD remains unclear, existing studies have shown that it is related to genetic susceptibility, gut microbiota disorder, destruction of the intestinal epithelial barrier, and abnormalities of the intestinal immune system (Goodman et al., 2020; Khor et al., 2011). Currently, the main clinical medicines for UC, such as salicylic acids, glucocorticoids, and immunosuppressants, focus on controlling intestinal inflammation. However, long-term or high doses of medication can prompt development of drug resistance and cause various adverse reactions in patients, ultimately failing to cure persistent UC (Bernstein, 2015; Grossberg et al., 2022).

In recent years, mucosal healing has been proposed as a therapeutic target for UC, and repair of the damaged intestinal barrier may be a solution for recurrent UC (Boal Carvalho and Cotter, 2017; Shah et al., 2016). A growing body of evidence has revealed that intestinal barrier dysfunction caused by a gut microbiota imbalance leads to UC (Gasaly et al., 2021). Small molecules metabolised by gut microbiota, including short-chain fatty acids, bile acids, and tryptophan metabolites, maintain the intestinal immune system and integrity of the intestinal barrier, serving as important intermediates for coordinating the microbiota-host interaction (Lavelle and Sokol, 2020; Scott et al., 2020). Alterations in these metabolites have been observed to be related to the occurrence of UC (Lavelle and Sokol, 2020; Lloyd-Price et al., 2019). Among them, some indole derivatives produced by microbial decomposition of tryptophan are the main endogenous ligands of the aryl hydrocarbon receptor (AhR), which is a ligand-activated transcription factor and an important regulator for maintaining homeostasis of the intestinal barrier (Pernomian et al., 2020; Scott et al., 2020). Activation of the AhR in lamina propria lymphocytes (mainly group 3 innate lymphoid cells, ILC3) promotes the production of IL-22, thereby regulating the intestinal immune response and protecting the function of the intestinal barrier (Li, Y.Y. et al., 2021). Notably, tryptophan levels in the faeces were significantly increased in UC patients and UC mice, indicating that tryptophan metabolism was impaired (Gupta et al., 2012; Jing et al., 2021). In addition, gut microbiota-related tryptophan metabolism is disrupted, resulting in decreased tryptophan metabolites and AhR activity in the intestinal tract, which eventually leads to reduced IL-22 production (Lamas et al., 2016, 2018). Therefore, the recovery of bacterial-related metabolites by gut microbiota regulation may be a strategy for repairing the intestinal barrier in UC.

Gegen Qinlian decoction (GQD) is a classic formula derived from Treatise on Febrile Diseases published in the Han Dynasty of Chinese history (202 BC–220 AD) for treating damp heat syndrome, protecting intestines and stopping diarrhoea (Zhang, 2005). It is composed of Pueraria lobata (Willd.) Ohwi (Gegen), Scutellaria baicalensis Georgi (Huangqin), Coptis chinensis French (Huanglian), and Glycyrrhiza uralensis Fisch (Gancao). The monarch drug Pueraria has antipyretic and antidiarrheal properties; the subject drugs Scutellaria and Coptis have a function to relieve damp heat and break stasis, and Glycyrrhiza can replenish qi (Wei et al., 2020). Glycyrrhizae uralensis Fisch. was included in the Russian Pharmacopoeia, United States pharmacopoeia of the legal drugs, and later included in Britain, France, Germany and many other countries pharmacopoeia (Shikov et al., 2021). By analyzing and summarizing the clinical trial literature of GQD in the treatment of UC published in common databases, the results showed that the average total effective rate of GQD in the treatment of UC was 92.4%, and the average cure rate was 47.2% (Wang et al., 2022). Other studies confirmed that GQD is effective against inflammatory intestinal diseases, including diarrhoea, ulcerative colitis, and intestinal adverse reactions caused by chemotherapeutic agents (Liu et al., 2019; Zhao et al., 2020). Animal studies have confirmed that GQD alleviates colitis in mice by repairing the damaged intestinal barrier and regulating the gut microbiota (Li et al., 2020; Wang et al., 2021), suggesting that there may be a relationship between these two components in the GQD treatment of UC. However, it is not completely clear whether GQD improves AhR-dependent intestinal barrier protection by regulating gut microbiota-related tryptophan metabolites in UC. Our study aimed to investigate whether and how gut microbiota-related tryptophan metabolism mediates the protective effects of GQD on the repair of damaged intestinal barrier.