In severe cirrhosis, RFX profoundly alters gut microbial composition by reducing pathobiont abundance while promoting rifampicin resistance in E. coli, and microbiota-derived signatures were associated with Child-Pugh scores, highlighting their potential to improve patient stratification.
Key Findings
Results
Rifaximin treatment reduced microbial richness in patients with severe cirrhosis over 12 months.
Study included 42 patients (21 RFX, 21 placebo) from the ProPILA-Rifax trial (NCT03069131)
Longitudinal gut microbiome characterization was performed using 16S rRNA gene sequencing over 12 months
Reduced microbial richness was observed in the rifaximin treatment group compared to placebo
Results
Rifaximin decreased the abundance of taxa typically enriched in advanced cirrhosis.
Taxa reduced by rifaximin treatment included Escherichia, Streptococcus, and Veillonella
These taxa are described as 'typically enriched in advanced cirrhosis' and are considered pathobionts
The reduction was characterized over a 12-month follow-up period using 16S rRNA gene sequencing
Results
Rifaximin treatment increased the proportion of Escherichia coli isolates exhibiting phenotypic resistance to rifampicin.
Resistance was assessed using culture-based phenotypic susceptibility testing
No cross-resistance to ciprofloxacin or cefotaxime was observed in rifaximin-treated patients
This finding was identified despite rifaximin being considered minimally absorbed and largely intraluminal in action
Results
In exploratory analyses, a decrease in Child-Pugh scores was correlated with enrichment of commensal taxa.
Child-Pugh score changes were used as a measure of disease severity over the study period
Enrichment of commensal taxa (rather than pathobionts) was associated with improvement in this clinical score
This finding suggests microbiota-derived signatures have potential to improve patient stratification
Results
Higher abundance of Ruminococcus bromii at inclusion was associated with improved 12-month survival.
This association was identified in exploratory analyses among the 42-patient cohort
Ruminococcus bromii is a commensal taxon associated with a healthier gut microbiome
The association was observed at baseline (inclusion), suggesting potential prognostic value of gut microbiome composition
Results
Higher abundance of Blautia obeum at inclusion was associated with a lower incidence of spontaneous bacterial peritonitis (SBP).
This association was identified in exploratory analyses
Blautia obeum is a commensal taxon; its higher abundance at baseline correlated with lower SBP incidence over 12 months
The parent trial (ProPILA-Rifax) evaluated rifaximin as primary prophylaxis of SBP in patients with severe cirrhosis
Methods
The study population consisted of patients with severe cirrhosis enrolled in the ProPILA-Rifax randomized trial.
42 patients total: 21 in the rifaximin arm and 21 in the placebo arm
This was an ancillary study of the ProPILA-Rifax trial (NCT03069131)
The trial evaluated rifaximin as primary prophylaxis of spontaneous bacterial peritonitis in patients with severe cirrhosis
Exploratory analyses assessed associations between bacterial profiles and clinical outcomes including disease severity, overall survival, and incidence of SBP
What This Means
This research examined how a commonly used antibiotic called rifaximin (RFX) — prescribed to people with severe liver scarring (cirrhosis) to prevent serious complications — affects the community of bacteria living in the gut. Using stool samples from 42 patients collected over 12 months, the researchers compared those who received rifaximin to those who received a placebo. They found that rifaximin significantly changed gut bacterial communities: it reduced the overall variety of bacteria and lowered the levels of certain harmful bacteria (such as Escherichia, Streptococcus, and Veillonella) that tend to overgrow in severe cirrhosis. However, rifaximin also caused more E. coli bacteria in the gut to become resistant to a related antibiotic, rifampicin, though this resistance did not extend to other commonly used antibiotics like ciprofloxacin or cefotaxime.
The study also found that the makeup of gut bacteria at the start of the study was linked to patient outcomes. Patients who had higher levels of certain 'good' bacteria — specifically Ruminococcus bromii and Blautia obeum — at the beginning of the study had better 12-month survival rates and lower risk of a dangerous complication called spontaneous bacterial peritonitis (SBP), respectively. Additionally, patients whose liver disease scores improved over time tended to have more beneficial, commensal bacteria in their guts.
This research suggests that the gut microbiome in cirrhosis patients is deeply connected to disease severity and clinical outcomes, and that rifaximin has a complex dual role: it reduces potentially harmful bacteria but also selects for antibiotic-resistant strains. The bacterial signatures identified here — particularly Ruminococcus bromii and Blautia obeum — may eventually help doctors identify which cirrhosis patients are at higher risk of complications, though further larger studies are needed to confirm these findings.
Ladeira R, Biguenet A, Meunier A, Gonthier M, Di Martino V, Pitta A, et al.. (2026). Gut microbial dynamics and antibiotic resistance during rifaximin therapy in severe cirrhosis: a ProPILA-Rifax ancillary study.. Frontiers in cellular and infection microbiology. https://doi.org/10.3389/fcimb.2026.1930709