Lung microbiome quantification and bacterial density as prognostic markers in lung transplantation

Chronic lung allograft dysfunction (CLAD) is a barrier to long-term survival following lung transplantation. Composition of the lung allograft microbiome has been explored as a prognostic marker for allograft survival, but most studies have measured bacterial relative, not absolute, abundances. Absolute quantitation of bacterial abundances improves the assessment of host-microbe interactions in diverse disease states and physiologic compartments but has not been compared to compositional indices alone for performance in identifying CLAD-associated allograft microbiomes.

We performed a case-control study to compare the composition of the lung allograft microbiome between lung transplant recipients who developed CLAD within the first 4 years of transplant (cases) versus those who remained CLAD-free for the first 5 years post-transplant (controls). Within 12 months post-transplantation, bronchoalveolar lavage fluid was collected from 53 cases and 55 controls to compare compositional features of the microbiome and bacterial absolute abundance.

We identified 5 overlapping compositional subtypes, termed community state types (CST), of the lung allograft microbiome that were dominated by either Prevotella species, Streptococcus and Neisseria species, Staphylococcus or Pseudomonas species, or a diverse bacterial population. Lower bacterial density was observed in the taxonomically diverse community and was lower in controls than cases. Normalizing the relative abundance of CST-defining bacteria to total bacterial density strengthened microbiome-composition/chronic lung allograft dysfunction (CLAD) associations.

Absolute bacterial quantification strengthens associations between the lung microbiome and CLAD following lung transplantation and may improve our understanding of how the lung microbiome affects lung transplant outcomes.