Acute Infection Disrupts the Respiratory Microbiome of Lung Transplant Recipients

Abstract

Respiratory infections are common after lung transplant and contribute to mortality and allograft failure. Studies suggest that respiratory infections alter the lung microbiome. We hypothesized that respiratory infections would be associated with a pathogenic bacteria dominating the microbiome community with ≥ 30% relative community abundance, and lower alpha diversity. A total of 152 bronchoalveolar lavage (BAL) samples were collected from 88 adult lung transplant recipients (LTR) between January 2017 - June 2018 as part of a single center retrospective study. Samples were categorized as "infected" or "surveillance" based on clinical data and were considered "infected" if 2 or more of the following criteria were met: recent fever, increased sputum, change in sputum appearance, increased shortness of breath, new radiographic infiltrate, or physician concern for infection. DNA was extracted, and bacterial 16S rRNA genes were amplified and sequenced. Sequences were classified taxonomically, and relative abundances were calculated. Comparative statistical analysis was performed using R. Of the 152 BAL samples, 19 (13%) were categorized as "infected". Infected samples were more likely than surveillance samples to be dominated by a single bacterial pathogen at ≥ 30% relative abundance (p=0.025) and ≥ 50% abundance (p=0.004) (Figure). Infected samples had a bacterial pathogen reach ≥ 30% relative abundance in 52% of samples, compared to 25% of the surveillance samples. Using a threshold of ≥ 50% abundance, infected samples had a dominant organism in 37% of samples compared to 10% of surveillance samples. Infected samples had lower mean alpha diversity than surveillance samples (Shannon index 14 vs. 19, p=0.03). Bacterial microbiota during respiratory infection was more likely to include a dominant bacterial pathogen than samples obtained in the absence of infection. Microbiota alpha diversity was also found to be reduced during respiratory infection.