Solid organ transplantation has emerged as a life-saving intervention for patients with end-stage diseases once deemed untreatable. While short-term success rates have improved significantly, enhancing long-term outcomes—such as survival and health-related quality of life—remains a key challenge. Emerging evidence suggests that the gut microbiome may play a critical role in modulating immune responses, graft tolerance, and overall recovery. However, the dynamics of gut microbiome development post-transplantation and its precise relationship with clinical outcomes remain poorly understood, warranting further investigation.**

In this thesis by Johann Swarte, we conducted comprehensive metagenomic sequencing of fecal samples obtained from two well-characterized cohorts: the TransplantLines cohort and biobank study at the University Medical Centre Groningen, and the Dutch Microbiome Project. Our analyses revealed that solid organ transplant recipients exhibit persistent gut dysbiosis, characterized by significantly reduced microbial diversity, an elevated presence of potentially pathogenic microbial species, and a marked decline in beneficial metabolic pathways. Furthermore, these individuals demonstrated a notable increase in both the prevalence and diversity of antibiotic resistance genes (ARGs) and microbial virulence factors. Strikingly, these alterations in the gut microbiome were not transient but remained evident for up to two decades following transplantation, highlighting the long-term impact of immunosuppression, antibiotic exposure, and altered host physiology on microbial ecology. These findings underscore the need for targeted microbiome-informed interventions to improve long-term transplant outcomes.

Comparative analyses with the general population demonstrate that gut dysbiosis is widespread among solid organ transplant recipients, including those who have undergone liver, kidney, lung, and heart transplants. This dysbiosis is not only characterized by disrupted microbial composition and function but is also strongly associated with poorer health-related quality of life and increased all-cause mortality. The transplant population, subject to continuous perturbations from lifelong immunosuppressive therapy, frequent antibiotic use, and a high burden of post-transplant comorbidities, represents a uniquely informative cohort for studying host–microbiome interactions. In this thesis, we identified extensive and clinically relevant associations between gut microbiome profiles and key post-transplant outcomes, suggesting that the microbiome may serve as both a biomarker and a modifiable factor in patient care. These findings hold significant translational promise for the development of personalized therapeutic strategies aimed at restoring microbial balance, reducing complications, and ultimately enhancing graft survival. By further unraveling the complex dynamics of the post-transplant gut microbiome, we open the door to innovative microbiome-based interventions that may revolutionize long-term transplant management and improve patient well-being.

Source: https://umcgresearch.org/w/the-gut-microbiome-of-solid-organ-transplant-recipients-translation-towards-improved-outcometra