Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation Journal Article
| Authors: | Harris, B.; Morjaria, S. M.; Littmann, E. R.; Geyer, A. I.; Stover, D. E.; Barker, J. N.; Giralt, S. A.; Taur, Y.; Pamer, E. G. |
| Article Title: | Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation |
| Abstract: | Rationale: 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. Objectives: To investigate whether changes in gut microbiota are associated with PCs after HCT. Methods: 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. Measurements and Main Results: 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 g-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 g-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). Conclusions: This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and g-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. © 2016 by the American Thoracic Society. |
| Keywords: | stem cell transplantation; microbiota; pulmonary disease |
| Journal Title: | American Journal of Respiratory and Critical Care Medicine |
| Volume: | 194 |
| Issue: | 4 |
| ISSN: | 1073-449X |
| Publisher: | American Thoracic Society |
| Date Published: | 2016-08-15 |
| Start Page: | 450 |
| End Page: | 463 |
| Language: | English |
| DOI: | 10.1164/rccm.201507-1491OC |
| PROVIDER: | scopus |
| PMCID: | PMC5003327 |
| PUBMED: | 26886180 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2016 -- Source: Scopus |
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