The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function
Raffaelle Girlanda,
Jedson R. Liggett,
Meth Jayatilake,
Alexander Kroemer,
Juan Francisco Guerra,
Jason Solomon Hawksworth,
Pejman Radkani,
Cal S. Matsumoto,
Michael Zasloff,
Thomas M. Fishbein
Affiliations
Raffaelle Girlanda
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Jedson R. Liggett
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Meth Jayatilake
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
Alexander Kroemer
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Juan Francisco Guerra
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Jason Solomon Hawksworth
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Pejman Radkani
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Cal S. Matsumoto
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Michael Zasloff
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
Thomas M. Fishbein
MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Center for Translational Transplant Medicine, Georgetown University, Washington, DC 20007, USA
We analyzed the fecal microbiome by deep sequencing of the 16S ribosomal genes and the metabolomic profiles of 43 intestinal transplant recipients to identify biomarkers of graft function. Stool samples were collected from 23 patients with stable graft function five years or longer after transplant, 15 stable recipients one-year post-transplant and four recipients with refractory rejection and graft loss within one-year post-transplant. Lactobacillus and Streptococcus species were predominant in patients with stable graft function both in the short and long term, with a microbiome profile consistent with the general population. Conversely, Enterococcus species were predominant in patients with refractory rejection as compared to the general population, indicating profound dysbiosis in the context of graft dysfunction. Metabolomic analysis demonstrated significant differences between the three groups, with several metabolites in rejecting recipients clustering as a distinct set. Our study suggests that the bacterial microbiome profile of stable intestinal transplants is similar to the general population, supporting further application of this non-invasive approach to identify biomarkers of intestinal graft function.
