• Jake G Natalini, Kendrew K Wong, Nathaniel C Nelson, Benjamin G Wu, Darya Rudym, Melissa B Lesko, Seema Qayum, Tyler C Lewis, Adrian Wong, Stephanie H Chang, Justin C Y Chan, Travis C Geraci, Yonghua Li, Chan Wang, Huilin Li, Prerna Pamar, Joseph Schnier, Ian J Mahoney, Tahir Malik, Fares Darawshy, Imran Sulaiman, Matthias C Kugler, Rajbir Singh, Destiny E Collazo, Miao Chang, Shrey Patel, Yaa Kyeremateng, Colin McCormick, Clea R Barnett, Jun-Chieh J Tsay, Shari B Brosnahan, Shivani Singh, Harvey I Pass, Luis F Angel, and Leopoldo N Segal.
• Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine.
• Am. J. Respir. Crit. Care Med. 2024 Jun 15; 209 (12): 146314761463-1476.

AbstractRationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

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