ABSTRACT
BACKGROUND AND AIMS: Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury. METHODS: Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries. RESULTS: Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury. CONCLUSIONS: Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury.
ABSTRACT
OBJECTIVE: Complications affect the outcome of patients with cirrhosis. The favorable prognosis of patients with Wilson disease (WD)-related cirrhosis suggests that its complications differ from those of hepatitis B virus (HBV) infection-related cirrhosis. We aimed to delineate the differences in complications between WD-related and HBV-related cirrhosis. METHODS: The electronic-medical data from patients with WD-related and HBV-related cirrhosis were extracted and analyzed. RESULTS: In total, 211 patients with WD-related cirrhosis and 374 patients with HBV-related cirrhosis were enrolled. Most patients with WD progressed to cirrhosis <10 years after disease onset, whereas those with HBV infection often progressed after >10 years. Patients with WD-related cirrhosis had a markedly lower prevalence of ascites (8.5% vs. 38.5%), gastroesophageal varices/variceal bleeding (13.3% vs. 47.6%), renal impairment (0 vs. 7.6%) and primary liver cancer (0 vs. 39.3%; all p < .001) than those with HBV-related cirrhosis. After adjustment for potential confounders, patients with WD-related cirrhosis carried a lower risk of varices/variceal bleeding. CONCLUSIONS: Although patients with WD progressed to cirrhosis much faster, the prevalence of complications from WD-related cirrhosis was low. Patients with WD-related cirrhosis were less likely to develop gastroesophageal varices/variceal bleeding than those with HBV-related cirrhosis.