Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Rationale</jats:title> <jats:p>Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>To investigate whether changes in gut microbiota are associated with PCs after HCT.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.</jats:p> </jats:sec> <jats:sec> <jats:title>Measurements and Main Results</jats:title> <jats:p>One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30–4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32–3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22–5.32; P = 0.015), and γ-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10–5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42–31.80; P = 0.016), whereas γ-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49–8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28–9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25–5.22; P = 0.009).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and γ-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.</jats:p> </jats:sec>