摘要
Aims:Previous studies have shown that hepatitis B virus(HBV)–related disease progression involves gut microbiota dysbiosis linked to inflammation,endotoxin translocation,and immune imbalance.While the artificial liver support system(ALSS)improves liver function and inflammation,its impact on the gut microbiome remains unclear.This study aimed to investigate changes in the gut microbiota of healthy individuals(healthy control[HC]group),patients with chronic hepatitis B(CHB group),patients with HBV-related acute-on-chronic liver failure(HBV-ACLF group),and patients after ALSS treatment.Methods:This single-center,prospective study enrolled 89 participants from the Infectious Disease Center of West China Hospital,Sichuan University,between October 2019 and December 2021,comprising the HC(n=11),CHB(n=24),HBV-ACLF(n=54),and ALSS(n=39 patients from the HBV-ACLF group who received three sessions of ALSS treatment)groups.We analyzed the diversity,composition,and characteristic microbial taxa of the gut microbiota under different disease con-ditions and evaluated the impact of ALSS treatment on gut microbiota dysbiosis.Fecal microbiota was analyzed by 16S ribosomal RNA sequencing.Microbial characteristics were assessed throughα-diversity(Chao1,Shannon,and Simpson indices)andβ-diversity(principal coordinate analysis).Statistical analysis was performed using the Kruskal–Wallis test,and the linear discriminant analysis(LDA)effect size(LEfSe)analysis was used to identify the characteristic microbial taxa among the different groups.Results:ALSS treatment significantly reduced serum total bilirubin(HBV-ACLF:370.64±113.13 vs.ALSS:203.08±118.70µmol/L,t=7.45,p<0.001),decreased creatinine levels(HBV-ACLF:107.14±55.45 vs.ALSS:82.43±57.16µmol/L,t=2.11,p=0.039),and modestly decreased albumin levels(HBV-ACLF:31.68±3.62 vs.ALSS:29.88±4.01 g/L,t=2.27,p=0.026).Microbial richness was significantly lower in the CHB group compared with HC(Chao1 index:W=198,p=0.018).Microbial diversity also declined,with Shannon and Simpson indices significantly reduced in the HBV-ACLF group compared with CHB(Shannon:W=898,p=0.007;Simpson:W=883,p=0.011),and similar reductions observed in the ALSS group(Shannon:W=643,p=0.013;Simpson:W=660,p=0.006).β-diversity analysis revealed distinct microbial community structures among groups(Adonis R2=0.98576,p=0.042).LEfSe analysis showed enrichment of Escherichia–Shigella and Enterococcus in HBV-ACLF,while ALSS reduced their relative abundance,suggesting a partial restoration of gut microbial balance.
基金
supported by the National Key Research and Development Program of China(No.2022YFC2304800)
1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC21014).
