Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain, discomfort, and altered defecation patterns (Ford et al., 2020). The prevalence of IBS is estimated to be 11.2% globally, with an incidence rate between 10% and 15% in China, Canada, and Australia (Lovell and Ford, 2012). The varying prevalence rates might be due to the different pathophysiologies of the condition and various potential risk factors such as genetics, gastrointestinal infections, diet, and gut microbiome, as well as the influence of psychological comorbidity. These factors may have different impacts on IBS depending on the geographical context (Black and Ford, 2020; Sperber et al., 2021). According to the Rome IV criteria, IBS can be classified into four subtypes: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS–C), mixed IBS (IBS-M), and unspecified type IBS (IBS–U) (Drossman, 2016). Among these subtypes, IBS-D is particularly prevalent and has a significant impact on the quality of life and work productivity of affected individuals (Ballou et al., 2019). However, the precise cause of IBS-D has not yet been fully understood, with genetic predisposition, environmental factors, altered gastrointestinal motility, gut microbiota dysregulation, and visceral hypersensitivity being implicated (Ford et al., 2020). Currently, there are several treatments available for IBS-D, including probiotics, antibiotics, immunosuppressive agents, 5-hydroxytryptamine antagonists, and fecal microbiota transplantation (Lacy et al., 2020). However, IBS-D has a complex pathogenesis with overlapping symptoms, and long-term drug use can cause adverse reactions leading to treatment failure. Therefore, developing more effective and safer therapeutic drugs is urgent for IBS-D.

Recent studies highlight the significant efficacy of traditional Chinese medicines (TCMs) in treating IBS-D with minimal side effects (Zheng et al., 2021). Linderae Radix, derived from the dried root of Lindera aggregata (Sims) Kosterm, boasts a rich history of treating gastrointestinal disorders marked by symptoms like abdominal pain, diarrhea, and abdominal discomfort (Lai et al., 2021). Modern pharmacological studies have reported that Linderae Radix's diverse bioactivities, including anti-inflammatory, analgesic, antimicrobial, and anti-tumor effects (Kuo et al., 2020; Yang et al., 2020). Importantly, our previous research confirmed that Linderae Radix water extract (LRWE) markedly alleviates the pathological symptoms of IBS-D rats. Notably, Linderae Radix can directly influence the gut microbiota, aiding in the prevention and treatment of related diseases (Lou et al., 2019; Tao et al., 2021). Emerging evidence highlights abnormal changes in gut microbiota closely associated with IBS-D (Hou et al., 2021; Linsalata et al., 2020), suggesting that understanding the pivotal role of gut microbiota could shed light on LRWE's mechanism in treating IBS-D.

The gut microbiota is recognized as an important “endocrine organ” and “metabolic organ”, playing a crucial role in maintaining the intestinal barrier function, immunity homeostasis, and influencing disease development (Gilbert et al., 2018). Furthermore, endogenous metabolites, co-metabolized by the “gut microbiota-host” interaction, including bile acids, short-chain fatty acids, vitamins, and tryptophan, exert significant impacts on intestinal homeostasis (Gao et al., 2018; Lavelle and Sokol, 2020). Previous studies have demonstrated that the intricate interplay between gut microbiota and host, alongside different metabolic pathways, represents potential treatment targets for IBS-D (Liu et al., 2019). However, the precise mechanism by which LRWE alleviates IBS-D through the regulation of gut microbiota composition and its metabolites has yet to be explored.

This study employed 16 S rRNA gene sequencing and LC-MS untargeted metabolomics techniques to investigate the impact of LRWE on the microbial communities in the cecal contents and serum metabolic profiles of rats with IBS-D. Spearman correlation analysis was used to integrate findings from differential gut microbiota and differential metabolites to gain a comprehensive understanding of LRWE's mechanism in the treatment of IBS-D. These insights offer potential diagnostic and therapeutic targets for further explorations.