The Gut Microbiome in End-stage Lung Disease and Lung Transplantation

Abstract

Abstract Background Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients but the gut microbiome of lung transplant recipients has not been previously studied. Methods We assessed the gut microbiome in 64 faecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analysed 243 faecal samples from age-, sex- and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analysed them in relation to the gut microbiome. Finally, we investigated the gut microbiome composition of lung transplant recipients in different chronic lung allograft dysfunction stages and longitudinal gut microbiome changes after transplantation. Results We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in chronic lung allograft dysfunction (CLAD) stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Conclusions Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation, including decreased microbial diversity, reduced abundances of important metabolic pathways and higher prevalence of antibiotic resistance genes and virulence factors.