Pulmonary Microbiome Changes in Lung Transplant Recipients with Gastroesophageal Reflux

Abstract

The pulmonary microbiome modulates the immune milieu in the lung allograft and is in turn influenced by external factors such as microaspiration of oropharyngeal contents. A potential driver of microaspiration is gastroesophageal reflux disease (GERD), which has been associated with poor outcomes after lung transplantation. We aimed to compare the pulmonary microbiome in lung transplant recipients with and without GERD, and correlate microbial composition with concurrent lung inflammation. We selected 22 GERD patients and 49 no-GERD controls from adult lung transplant recipients with 24-hour pH-impedance testing and bronchoalveolar lavage fluid (BAL) collection at 3 months post-transplant. BAL microbial communities were characterized by 16S rRNA gene sequencing. Ten inflammatory protein markers in BAL were measured by multiplex assay. Baseline patient characteristics including age, sex, primary disease, and transplant type were comparable between GERD and no-GERD groups. Shannon diversity index was lower (MD=-0.33, p=0.04), while Berger-Parker dominance index was higher (MD=0.10, p=0.03), in GERD patients compared to no-GERD controls. Hierarchical clustering of all samples by Bray-Curtis dissimilarity identified three distinct pneumotypes (Figure 1). GERD was significantly associated with one of these pneumotypes, PT1, which was enriched in multiple anaerobic oropharyngeal taxa including Prevotella and Veillonella. In GERD patients, the presence of PT1 compared to all others was associated with higher levels of IL-8 (p=0.03). At time of GERD diagnosis, lung transplant recipients are more likely to have a pulmonary microbiome lower in diversity and enriched in oropharyngeal taxa. These perturbations are consistent with microaspiration and may contribute to allograft inflammation. Future studies are warranted to assess how the pulmonary microbiome changes over time in the context of GERD and its correlation with rejection and long-term outcomes.