Gut-liver axis dysregulation in colitis underlies structure-dependent pharmacokinetics of a traditional Chinese medicine
Abstract
Pharmacokinetic (PK) variability under pathological conditions poses challenges for drug efficacy and safety. Although clinical data comparing PK in healthy individuals and patients is limited, evidence suggests that disease-induced variability is common and clinically significant. The liver and gut microbiota are key contributors to this variability, yet their individual and combined roles-particularly via the gut-liver axis-remain unclear, especially for complex herbal medicines. Ulcerative colitis (UC), characterized by immune dysregulation, gut microbiota dysbiosis, and hepatic inflammation, provides a relevant model to study these interactions. In this study, we investigated how UC-induced alterations in liver metabolism and gut microbiota affect the PK profiles of a multi-component herbal formula. Comparative analysis between healthy and colitis mice revealed structure-dependent PK shifts: iridoids and flavonoids exhibited reduced systemic exposure (e.g., 0.82-fold change in AUC for loganin), while saponins and polyphenols demonstrated altered colonic availability. Additionally, alkaloids showed delayed systemic elimination (e.g., 5.81-fold change in T1/2 for berberine). Multi-omics profiling identified disruptions along the gut-liver axis, including downregulated hepatic enzymes (CYPs, UGTs) and microbial changes such as 125% increased glycoside hydrolases (GHs). Specific compounds-berberine, liquiritin, and glycyrrhizic acid-were influenced by both hepatic and…
Read the paper
Related studies
- Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids
- Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome
- Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with Crohn's disease
- Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model
- Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research
- Glyphosate-based herbicides influence antioxidants, reproductive hormones and gut microbiome but not reproduction: A long-term experiment in an avian model
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.