Gut microbial dynamics and antibiotic resistance during rifaximin therapy in severe cirrhosis: a ProPILA-Rifax ancillary study
8 affiliations
- 1Bioinformatique et Big Data Au Service de La Santé, Oncobiologie Génétique Bioinformatique, Centre Hospitalier Universitaire (CHU) Besançon Franche-Comté , ,
- 2Hygiène Hospitalière, Centre Hospitalier Universitaire (CHU) Besançon Franche-Comté , ,
- 3Université Marie et Louis Pasteur, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 6249 Chrono-environnement , ,
- 4Université Marie et Louis Pasteur, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1098 Regulation of Immunity for therapeutic innovation in Graft, Host, Tumoral and inflammatory-associated diseases (RIGHT) , ,
- 5Service d’Hépato-Gastroentérologie, Hôpital Cabrol , ,
- 6Univ. Rennes, Centre Hospitalier Universitaire (CHU) Rennes, Service des Maladies du Foie, Institut National de la Santé et de la Recherche Médicale (INSERM) 1241 Nutrition, Métabolismes et Cancer (NUMECAN) , ,
- 7Department of Bacteriology, Rennes University Hospital , ,
- 8Centre d’Investigation Clinique 1431, unité de METhodologie (uMETh), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Besançon Franche-Comté , ,
Abstract
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.
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BibTeX
@article{ladeira2026microbial,
title = {{Gut microbial dynamics and antibiotic resistance during rifaximin therapy in severe cirrhosis: a ProPILA-Rifax ancillary study}},
author = {Ruben Ladeira and Adrien Biguenet and Alexandre Meunier and Marion Gonthier and Vincent Di Martino and Anaïs Pitta and Edouard Bardou-Jacquet and Anne Jolivet-Gougeon and Maxime Desmarets and Thierry Thévenot and Didier Hocquet and Benoit Valot},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = sep,
doi = {10.3389/fcimb.2026.1930709},
url = {https://europepmc.org/article/PMC/PMC13658500},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut microbial dynamics and antibiotic resistance during rifaximin therapy in severe cirrhosis: a ProPILA-Rifax ancillary study
AU - Ruben Ladeira
AU - Adrien Biguenet
AU - Alexandre Meunier
AU - Marion Gonthier
AU - Vincent Di Martino
AU - Anaïs Pitta
AU - Edouard Bardou-Jacquet
AU - Anne Jolivet-Gougeon
AU - Maxime Desmarets
AU - Thierry Thévenot
AU - Didier Hocquet
AU - Benoit Valot
PY - 2026
DA - 2026/09/29
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1930709
UR - https://europepmc.org/article/PMC/PMC13658500
AB - 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.
SN - 2235-2988
ER -