Microbiota and Immune Regulation in Lung Transplantation

Abstract Purpose of the Review The lung and gut microbiomes have been associated with many important patient-centered outcomes in respiratory diseases, and these have been further associated with pulmonary immunity. Lung transplant patients are necessarily unique with regards to their microbiome characteristics and their immune responses. The goal of this review is to summarize the emerging literature relevant to of bidirectional relationship of the microbiome and pulmonary immunity, with a focus on data relevant to lung transplant recipients. Recent Findings Lung transplant patients tend to have increased lung bacterial burden and shifts in microbial community composition relative to healthy controls. These lung microbiome changes are linked to important post-transplant outcomes, including primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction. Furthermore, these lung microbiome characteristics—especially having an increased lung bacterial burden or communities dominated by “pathogenic” taxa are associated with a pro-inflammatory pulmonary immune signals in lung transplant patients, despite their concurrent use of immunosuppression. The gut microbiome, through systemic pathways such as short-chain fatty acid (SCFA) production, also appears to influence pulmonary immunity in non-transplant patients, although its role in lung transplant recipients remains underexplored. Summary The lung microbiome remains an important factor in pulmonary immunity after lung transplantation, and the gut microbiome has been implicated as further impacting pulmonary and systemic immunity in non-transplant population. Microbiome-targeted interventions show promise—especially in selected populations—but have not yet been linked with improved patient-centered outcomes. Further research which incorporates adequate clinical context is needed to disentangle which microbiome features and immune signals might be harnessed or targeted to optimize post-transplant care and prolong allograft survival.