Microbiome compositions and fecal metabolite concentrations predict post-operative infection in liver transplant recipients

BackgroundLiver transplantation (LT) is associated with postoperative infections caused by antibiotic-resistant bacterial pathogens that reside in the intestine. An intact intestinal microbiome suppresses expansion of enteric pathogens, however patients with severe liver disease often have reduced microbiome diversity and increased density of antibiotic-resistant Enterococcus and Enterobacterales species. (1-4) Experimental models have demonstrated that metabolites produced by the intestinal microbiome, including short chain fatty acids (SCFAs), secondary bile acids and indole compounds, enhance host epithelial and immune defenses against enteric pathogens.(5-10) Microbiome derived metabolites likely contribute to resistance against infectious diseases in LT patients, however, this remains uninvestigated. MethodsWe prospectively enrolled 107 liver transplant candidates and determined peri-transplant fecal microbiome compositions including relative and absolute fecal metabolite concentrations. ResultsFecal microbiomes in LT recipients ranged from highly diverse to complete loss of diversity resulting in expansion of Enterococcus and/or Enterobacterales species that were associated with postoperative infection. Gas chromatographic (GC-) and liquid chromatographic (LC-) Mass spectrometric analyses revealed decreased concentrations of SCFAs, secondary bile acids, and indole compounds in fecal samples with low microbiome diversity and associated expansion of Enterococcus and Enterobacterales populations. ConclusionFecal metabolite abundances accurately predicted LT patients with reduced microbial diversity and those who developed postoperative infection.