Microbiome alterations following solid-organ transplantation: consequences, solutions, and prevention

Abstract

Microbiome alterations following solid-organ transplantation: consequences, solutions, and prevention Hannah P Rahim,1,2,* Michael R Taylor,1,2,* Simon A Hirota,3 Steven C Greenway1,2,4 1Department of Pediatrics, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, 2Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3Department of Pharmacology and Physiology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, 4Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada *These authors contributed equally to this work Abstract: Improved long-term survival following solid-organ transplantation (SOT) has remained elusive over the past several decades, despite significant advances in early survival. The microbiome refers to the genetic material belonging to microbes that live in an ecological balance with the human host, and its importance in human health is increasingly recognized. Extensive research pertaining to the human microbiome has demonstrated that compositional changes in the microbiome can contribute to such diseases as inflammatory bowel disease, metabolic syndrome, and (recently) many of the comorbidities that develop after SOT. It is suggested that the microbiome may be an important environmental variable that could influence health outcomes after SOT. Many factors related to SOT, including end-stage organ disease, surgery, and the use of antimicrobial prophylaxis and immunosuppressive drugs, have been shown to affect microbial composition and function negatively. These alterations could compromise health outcomes after SOT through the dysregulation of important host–microbe interactions, including the modulation of local and systemic host immune function by the gut microbiome, and could contribute to morbidity and even allograft rejection. Such interventions as synbiotic therapy and fecal microbiota transplantation have the potential to prevent or reverse disruption of the microbiome related to SOT and thereby improve the longevity of transplant recipients. Although microbiome research is still a relatively new field, progress is accelerating exponentially. Future research on host–­microbiome interactions in the context of SOT will facilitate the development of microbiome-directed treatments to improve patient outcomes on pre- and post-SOT. Keywords: transplantation, immunosuppression, dysbiosis, immune system, microbiome