Gut microbial dynamics and antibiotic resistance during rifaximin therapy in severe cirrhosis: a ProPILA-Rifax ancillary study

Introduction Increasing evidence implicates gut dysbiosis in the pathophysiology of advanced cirrhosis. This is an ancillary study of the ProPILA-Rifax trial (NCT03069131), which evaluated rifaximin (RFX) as primary prophylaxis of spontaneous bacterial peritonitis (SBP) in patients with severe cirrhosis. Although the combined use of RFX and lactulose is effective in preventing recurrent hepatic encephalopathy (HE), its longitudinal impact on microbial communities and antibiotic resistance remains poorly characterized. Methods We characterized longitudinal changes in the gut microbiome of 42 patients (21 RFX, 21 placebo) over 12 months using 16S rRNA gene sequencing and culture-based phenotypic susceptibility testing. Exploratory analyses between patient bacterial profiles and clinical outcomes (disease severity, overall survival, and incidence of SBP) were conducted. Results RFX treatment reduced microbial richness and decreased the abundance of taxa typically enriched in advanced cirrhosis (e.g., Escherichia , Streptococcus , Veillonella ). RFX increased the proportion of Escherichia coli isolates exhibiting phenotypic resistance to rifampicin, without observed cross-resistance to ciprofloxacin or cefotaxime. In exploratory analyses, a decrease in Child-Pugh scores was correlated with enrichment of commensal taxa. Moreover, higher abundances of Ruminococcus bromii and Blautia obeum at inclusion were respectively associated with improved 12-month survival and a lower incidence of SBP. Discussion In severe cirrhosis, RFX profoundly alters gut microbial composition by reducing pathobiont abundance while promoting rifampicin resistance in E. coli . Furthermore, microbiota-derived signatures were associated with Child-Pugh scores, highlighting their potential to improve patient stratification.