Colonizing multidrug-resistant bacteria and the longitudinal evolution of the intestinal microbiome after liver transplantation

Nat Commun. 2019 Oct 17;10(1):4715. doi: 10.1038/s41467-019-12633-4.

Abstract

Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysbiosis after LT remain unclear. We prospectively recruited 177 adult patients undergoing LT at a single tertiary care center. 16 S V3-V4 rRNA sequencing was performed on 723 fecal samples collected pre-LT and periodically until one-year post-LT to test whether MDRB colonization was associated with decreased microbiome diversity. In multivariate linear mixed-effect models, MDRB colonization predicts reduced Shannon α-diversity, after controlling for underlying liver disease, antibiotic exposures, and clinical complications. Importantly, pre-LT microbial markers predict subsequent colonization by MDRB. Our results suggest MDRB colonization as a major, previously unrecognized, marker of persistent dysbiosis. Therapeutic approaches accounting for microbial and clinical factors are needed to address post-transplant microbiome health.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / classification
  • Bacteria / drug effects
  • Bacteria / genetics
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Dysbiosis / genetics
  • Dysbiosis / microbiology
  • Dysbiosis / prevention & control
  • End Stage Liver Disease / microbiology
  • End Stage Liver Disease / therapy*
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Humans
  • Liver Transplantation / methods*
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Ribosomal, 16S / genetics

Substances

  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S