Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation

Abstract

Organ transplantation is a life-saving treatment for patients with end-stage disease, but survival rates after transplantation vary considerably. There is now increasing evidence that the gut microbiome is linked to the survival of patients undergoing hematopoietic cell transplant, yet little is known about the role of the gut microbiome in solid organ transplantation. We analyzed 1370 fecal samples from 415 liver and 672 renal transplant recipients using shotgun metagenomic sequencing to assess microbial taxonomy, metabolic pathways, antibiotic resistance genes, and virulence factors. To quantify taxonomic and metabolic dysbiosis, we also analyzed 1183 age-, sex-, and body mass index–matched controls from the same population. In addition, a subset of 78 renal transplant recipients was followed longitudinally from pretransplantation to 24 months after transplantation. Our data showed that both liver and kidney transplant recipients suffered from gut dysbiosis, including lower microbial diversity, increased abundance of unhealthy microbial species, decreased abundance of important metabolic pathways, and increased prevalence and diversity of antibiotic resistance genes and virulence factors. These changes were found to persist up to 20 years after transplantation. Last, we demonstrated that the use of immunosuppressive drugs was associated with the observed dysbiosis and that the extent of dysbiosis was associated with increased mortality after transplantation. This study represents a step toward potential microbiome-targeted interventions that might influence the outcomes of recipients of solid organ transplantation.

Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease

“…In solid organ transplant recipients, the use of immunosuppressive drugs was the single most important determinant of microbiome damage, that lasted for years after transplantation. 46 In allogeneic HCT, the microbiome was demonstrated to affect the recovery of innate and adaptive immunity in general and T cell recovery specifically, reinforcing the reciprocal nature of the interaction between the immune system and the microbiome. 47 , 48 …”

Early immunomodulatory program triggered by pro-tolerogenicBifidobacterium pseudolongumdrives cardiac transplant outcomes

“…These observations strongly suggest that immune analyses require a detailed appreciation of several major variables and an assessment of both short and long-term changes. In particular, for microbiota-informed interventions, longitudinal monitoring of bacteria colonization and consideration of repeated administration may be critical to ensure a long term biotherapeutic effect [53, 58].…”

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

“…While this has been well known for decades [240][241][242], recent research employing novel research tools [243][244][245][246][247][248][249][250][251][252][253] has uncovered interactions between brain and immune system at unprecedented resolution. Similiarly, advanced molecular genetic methods [182,[254][255][256][257][258][259] contributed to elucidate mechanistic pathways linking the GIT microbiome to the systemic innate immune response with its impact upon cardiovascular [260,261] and neurological diseases [262,263]. Below we try to assess the clinical translational status of these research fields, focusing on therapeutic modulation of stress-induced disturbed brain -immune system interactions (section 4.1), and of the GIT microbiome and its products (section 4.2).…”