Journal
BLOOD
Volume 131, Issue 26, Pages 2978-2986Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2018-01-828996
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Funding
- National Institutes of Health, National Institute of Allergy and Infectious Diseases [UO1 AI124275, RO1 AI095706, RO1 AI42135]
- National Cancer Institute [P30 CA008748, PO1 CA023766]
- Cycle for Survival to the MSK Center for Microbes, Inflammation and Cancer
- Parker Institute for Cancer Immunotherapy at MSKCC
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Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio 5 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.
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