Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection
Authors
Christopher J. Lehmann, Department of Medicine, Section of Infectious Disease and Global Health, University of Chicago Medicine, 5841 S. Maryland Ave., Chicago, IL 60637, USA; Department of Pediatrics, Section of Pediatric Infectious Diseases, University of Chicago Medicine, 5841 S. Maryland Ave., Chicago, IL 60637, USA. Electronic address: christopher.lehmann@bsd.uchicago.edu.
Nicholas P. Dylla, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Matthew Odenwald, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL 60637, USA.
Ravi Nayak, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Maryam Khalid, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Jaye Boissiere, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Jackelyn Cantoral, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Emerald Adler, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Matthew R. Stutz, Department of Pulmonary and Critical Care Medicine, Cook County Health, 1950 W. Polk St, Chicago, IL 60612, USA.
Mark Dela Cruz, Advocate Aurora HealthFollow
Angelica Moran, Department of Pathology, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL 60637, USA.
Huaiying Lin, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Ramanujam Ramaswamy, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Anitha Sundararajan, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Ashley M. Sidebottom, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Jessica Little, Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA.
Eric G. Pamer, Department of Medicine, Section of Infectious Disease and Global Health, University of Chicago Medicine, 5841 S. Maryland Ave., Chicago, IL 60637, USA; Duchossois Family Institute, Biological Sciences Division, University of Chicago, 900 E. 57th St, Chicago, IL 60637, USA. Electronic address: egpamer@bsd.uchicago.edu.
Andrew Aronsohn, Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL 60637, USA.
John Fung, Department of Surgery, Section of Transplant Surgery, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL 60637, USA.
Talia B. Baker, Department of Surgery, Division of Transplantation and Advanced Hepatobiliary Surgery, University of Utah Health, 30 N. 1900 East, Salt Lake City, UT 84132, USA.
Aalok Kacha, Department of Anesthesia and Critical Care, University of Chicago Medicine, 5841 South Maryland Ave, Chicago, IL 60637, USA. Electronic address: akacha@bsd.uchicago.edu.
Recommended Citation
Lehmann CJ, Dylla NP, Odenwald M, et al. Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection. Cell Host Microbe. 2024;32(1):117-130.e4. doi:10.1016/j.chom.2023.11.016
Abstract
Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.
