Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation

Lung injury is a known complication of hematopoietic cell transplantation (HCT), often fatal. This study used bronchoalveolar lavage (BAL) fluid samples from 229 pediatric HCT patients to identify high-risk BAL compositions associated with in-hospital mortality. Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation, and commensal depletion with viral/staphylococcal enrichment, lymphocytic activation, and cellular injury. These findings were replicated in an independent cohort. Antibiotic exposure was linked to commensal depletion and enrichment of viruses and fungi. These interactions clarify drivers of fatal lung injury, suggesting potential for personalized diagnostics and treatments to improve HCT outcomes.

Matt S. Zinter, Christopher C. Dvorak, Madeline Y. Mayday, Gustavo Reyes, Miriam R. Simon, Emma M. Pearce, Hanna Kim, Peter J. Shaw, Courtney M. Rowan, Jeffrey J. Auletta, Paul L. Martin, Kamar Godder, Christine N. Duncan, Nahal R. Lalefar, Erin M. Kreml, Janet R. Hume, Hisham Abdel-Azim, Caitlin Hurley, Geoffrey D. E. Cuvelier, Amy K. Keating, Muna Qayed, James S. Killinger, Julie C. Fitzgerald, Rabi Hanna, Kris M. Mahadeo, Troy C. Quigg, Prakash Satwani, Paul Castillo, Shira J. Gertz, Theodore B. Moore, Benjamin Hanisch, Aly Abdel-Mageed, Rachel Phelan, Dereck B. Davis, Michelle P. Hudspeth, Greg A. Yanik, Birgitta A. Versluys, Caroline A. Lindemans, Jaap J. Boelens, Joseph L. DeRisi