Microbiota profiling to predict clinical events post-heart transplantation 3122

Abstract Description Human studies have correlated changes in microbiota profiles with clinical outcomes including allograft rejection and postoperative infection, but these data exist mostly outside of heart transplantation (HT). The impact of the microbiota and any identified microbial taxa in these clinical HT outcomes is not clear. We have previously identified distinct microbial composition and reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from HT recipients compared to healthy donors. Here, we investigated the relationship between peri-transplant fecal microbial composition and postoperative infection risk. Metagenomic sequencing was used to determine peri-transplant fecal microbiota profiles of 121 HT recipients and infections occurring in the first 100 days following transplantation were aggregated. We found a strong correlation between reduced gut microbial diversity and incidence of postoperative infection. Notably, patients who developed infections had an expansion of potentially pathogenic taxa, while uninfected patients had more abundant obligate anaerobic taxa. Preliminary data suggests a potential causal relationship between reduced microbial diversity and increased susceptibility to/severity of systemic infection in mice. Further metabolomic profiling may identify additional causative mechanisms for infection and help develop strategies to preserve or restore the microbiome of HT patients. Funding Sources Supported by NIH/NIAID T32AI007090; NIH/NIAID R01 AI115716; UChicago DFI Multidisciplinary Grant Topic Categories Transplantation Immunology (TRAN)