Journal
TRANSLATIONAL RESEARCH
Volume 186, Issue -, Pages 79-94Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.trsl.2017.06.008
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Funding
- University of Luxembourg (ImMicroDyn1) - Luxembourg National Research Fund (FNR)
- ATTRACT program grant - Luxembourg National Research Fund (FNR) [ATTRACT/A09/03]
- European Union Joint Programming in Neurodegenerative Disease grant - Luxembourg National Research Fund (FNR) [INTER/JPND/12/01]
- CORE grant - Luxembourg National Research Fund (FNR) [CORE/15/BM/10404093]
- Aide a la Formation Recherche grants - Luxembourg National Research Fund (FNR) [AFR PHD/4964712, AFR PHD-2013-5824125, AFR PHD-2014-1/7934898]
- CORE junior - Luxembourg National Research Fund (FNR) [C15/SR/10404839]
- Luxembourg National Research Fund (FNR) [PoC/13/02]
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In patients undergoing allogeneic hematopoietic stem cell transplantation.(allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or conse-quential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria,and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An Integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the Post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coil strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in personalizing'' regimens for individual patients to improve overall outcomes.
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