The gut microbiome of solid organ transplant recipients translation towards improved outcome

Solid organ transplantation has become a vital solution for treating patients with end-stage disease who were previously considered untreatable. Long-term outcomes such as health related quality of life and survival can still be improved. How the gut microbiome develops after solid organ transplantation and how the gut microbiome relates with outcomes was unknown. We performed metagenomic sequencing of faecal samples from two cohorts, the TransplantLines cohort and biobank study from the University Medical Centre Groningen and the Dutch microbiome project. Solid organ transplant recipients suffer 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 for up to 20 years after transplantation. Comparison with the general population reveals that dysbiosis is present in a large number of transplantation patients including liver-, renal, lung- and heart transplant recipients. The extent of dysbiosis is associated with lower health related quality of life and increased mortality. Constant perturbation due to the use of immunosuppressive drugs, antibiotics and post-transplantation comorbidities make transplant recipients a fascinating population to study the gut microbiome. The extensive associations observed in this thesis have translational potential towards personalized and optimized treatments that harness the power of the gut microbiome. By delving deeper into this microbial cosmos, we can uncover innovative approaches to enhance transplantation outcomes, mitigate complications and promote long-term graft acceptance.