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Review
. 2021 Aug;40(8):733-744.
doi: 10.1016/j.healun.2021.04.014. Epub 2021 May 7.

The lung microbiome in lung transplantation

John E McGinniss  1 , Samantha A Whiteside  1 , Aurea Simon-Soro  2 , Joshua M Diamond  1 , Jason D Christie  3 , Fredrick D Bushman  4 , Ronald G Collman  5
Affiliations
Review

The lung microbiome in lung transplantation

John E McGinniss et al. J Heart Lung Transplant. 2021 Aug.

Abstract

Culture-independent study of the lower respiratory tract after lung transplantation has enabled an understanding of the microbiome - that is, the collection of bacteria, fungi, and viruses, and their respective gene complement - in this niche. The lung has unique features as a microbial environment, with balanced entry from the upper respiratory tract, clearance, and local replication. There are many pressures impacting the microbiome after transplantation, including donor allograft factors, recipient host factors such as underlying disease and ongoing exposure to the microbe-rich upper respiratory tract, and transplantation-related immunosuppression, antimicrobials, and postsurgical changes. To date, we understand that the lung microbiome after transplant is dysbiotic; that is, it has higher biomass and altered composition compared to a healthy lung. Emerging data suggest that specific microbiome features may be linked to host responses, both immune and non-immune, and clinical outcomes such as chronic lung allograft dysfunction (CLAD), but many questions remain. The goal of this review is to put into context our burgeoning understanding of the lung microbiome in the postlung transplant patient, the interactions between microbiome and host, the role the microbiome may play in post-transplant complications, and critical outstanding research questions.

Keywords: chronic lung allograft dysfunction; hostmicrobe interactions; lung microbiome; lung transplantation.

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Figures

Figure 1.
Figure 1.. Factors contributing to lung dysbiosis following transplantation.
(1) The upper respiratory tract microbiome is the source of lung bacteria in health and is markedly dysbiotic both in people with advanced lung disease awaiting transplantation and patients post-transplant. (2) Microbial entry to the lung occurs via microaspiration, which is increased in post-transplant subjects. (3) Recipients’ microbiota seed the allograft from large airway colonization, particularly in cystic fibrosis and related conditions, or via dysbiosis in the native lung in single lung transplantation. (4) The donor lung may bring an endogenous microbiome along with it. (5) Mechanical clearance is disrupted in transplant recipients through mucociliary dysfunction, anastomosis site barriers, disrupted afferent loop of the cough reflex, lymphatic disruption. (6) Immune clearance is impeded by immunosuppressive treatment and disrupted lymphatics. (7) Local replication in the lung is increased compared with healthy people, with greater divergence (beta-diversity) between URT and lung microbiome communities. (8) The pressure exerted by frequent or continuous antimicrobial treatment may alter the microbiome in ways that remain to be determined.
Figure 2.
Figure 2.. Host-microbiome interactions after lung transplantation.
Emerging evidence supports cross-talk between the lung microbiome and host responses after transplantation. While data is still evolving, the lung microbiome composition has been implicated in regulating basal immune tone and host response to resident microbiota and pathogens through cellular components like myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), cytokines and chemokines, and other pathways (acetylated proline-glycine-proline (Ac-PGP); cyclooxygenase (COX)). Distinct microbiome profiles have also been linked to remodeling and fibrosis pathways that may contribute to post-transplant injury via multiple cytokines, growth factors, metalloproteinases, and collagen and matrix proteins. Additional abbreviations: Platelet-derived growth factor receptor-D, PDGFR-D; interleukin, IL; tumor necrosis factor-alpha, TNF-a; interferon gamma-induced protein-10, IP-10; matrix metalloproteinase, MMP; insulin-like growth factor-1, IGF-1
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