Purpose: Host-microbiota interactions can modulate the immune system at local and systemic levels with potential consequences for organ transplantation outcomes.However,the precise nature of these interactions and their health consequences still remain to be defined.In this study,we hypothesized that differences in urinary microbiota following kidney transplant would be associated with post-transplantation status between STAble,Minimally ImmunoSuppressed and TOLerant patients.
Methods: 113 urine samples were collected 6 months to 31 years after kidney transplantation from STA,MIS,TOL and Healthy Volunteers.Urinary microbiota 16S rRNA genes were sequenced and analyzed with Simpson and Shannon indices and principal component analyses of unweighted UniFrac distances.OTUs comparison were assessed between STA,TOL,MIS and HV.
Results: TOL and STA featured a significant increase in bacterial community and biodiversity compared to HV.TOL recipients were also characterized by higher relative abundance of Proteobacteria at phyla and families levels compared to STA and MIS.Furthermore, Lactobacillales and Bacillales (Firmicutes) were significantly associated with TOL and negatively correlated with CNI and mTOR inhibitors.This specific and unique microbiota profile was stable over time.
Discussion: The higher relative abundance of specific bacterial phyla and families from Proteobacteria or Firmicutes may favor stability/tolerance to the graft over time.Immunosuppressive drugs were likey to impact microbial diversity and metabolic functions with distinct profiles according to transplant status.It remains to establish whether tolerance was responsible for this microbiota profile and/or inversely.Dissecting these interactions would allow for new ways to diagnose and treat immunological disorders and promote tolerance in transplantation.
Luc Colas– Allergist and clinical immunologist, MD ; PhD student, CHU de Nantes ; Inserm
Emmanuel Mongodin– firstname.lastname@example.org
Emmanuel Montassier– CHU de Nantes
Mélanie Chesneau– post-doctorate, CRTI UMR1064, INSERM, Université de Nantes
Pierrick Guerrif– CHU de Nantes
Lauren Hittle– University of Maryland School of Medicine
Magali Giral– PU-PH, CRTI UMR1064, INSERM, Université de Nantes
Jonathan Bromberg– University of Maryland School of Medicine
Sophie Brouard– Centre de Recherche en Transplantation et Immunologie (CRTI) UMR 1064, INSERM, Université de Nantes, ITUN, CHU de Nantes