Early E. Casseliflavus gut colonization and outcomes of allogeneic hematopoietic cell transplantation

Armin Rashidi, Maryam Ebadi, Robin R. Shields-Cutler, Kathryn Kruziki, Dawn A Manias, Aaron M Barnes, Todd E De For, Patricia Ferrieri, Jo-Anne H Young, Dan Knights, Bruce R Blazar, Daniel J Weisdorf, Gary M Dunny

Research output: Contribution to journalArticle

Abstract

Gut dysbiosis has been associated with worse allogeneic hematopoietic cell transplantation (allo-HCT) outcomes. We reported an association between intrinsically vancomycin-resistant enterococci (iVRE: E. gallinarum and E. casseliflavus) gut colonization and lower post-transplant mortality. In this study, using an expanded cohort, we evaluated whether our previously observed association is species-specific. We included allo-HCT recipients with 1 positive rectal swab or stool culture for iVRE between days -14 and +14 of transplant. To investigate whether iVRE modulate the gut microbiota, we performed agar diffusion assays. To investigate whether iVRE differ in their ability to activate the aryl hydrocarbon receptor, we analyzed iVRE genomes for enzymes in the shikimate and tryptophan pathways. Sixty six (23 E. casseliflavus and 43 E. gallinarum) of the 908 allograft recipients (2011–2017) met our inclusion criteria. Overall survival was significantly higher in patients with E. casseliflavus (91% vs. 62% at 3 years, P = 0.04). In multivariable analysis, E. casseliflavus gut colonization was significantly associated with reduced all-cause mortality (hazard ratio 0.20, 95% confidence interval 0.04–0.91, P = 0.04). While agar assays were largely unremarkable, genome mining predicted that E. casseliflavus encodes a larger number of enzymes in the tryptophan metabolism pathway. In conclusion, E. casseliflavus gut colonization is associated with reduced post-HCT morality. Further research is needed to understand the mechanisms for this association.

Original languageEnglish (US)
Article numbere0220850
JournalPloS one
Volume14
Issue number8
DOIs
StatePublished - Jan 1 2019

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cell transplantation
Cell Transplantation
Tryptophan
Agar
Transplants
digestive system
Dysbiosis
Association reactions
Genome
Aryl Hydrocarbon Receptors
Aptitude
Mortality
Assays
Enzymes
Genes
tryptophan
Allografts
agar
Confidence Intervals
Vancomycin

PubMed: MeSH publication types

  • Journal Article

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Early E. Casseliflavus gut colonization and outcomes of allogeneic hematopoietic cell transplantation. / Rashidi, Armin; Ebadi, Maryam; Shields-Cutler, Robin R.; Kruziki, Kathryn; Manias, Dawn A; Barnes, Aaron M; De For, Todd E; Ferrieri, Patricia; Young, Jo-Anne H; Knights, Dan; Blazar, Bruce R; Weisdorf, Daniel J; Dunny, Gary M.

In: PloS one, Vol. 14, No. 8, e0220850, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Gut dysbiosis has been associated with worse allogeneic hematopoietic cell transplantation (allo-HCT) outcomes. We reported an association between intrinsically vancomycin-resistant enterococci (iVRE: E. gallinarum and E. casseliflavus) gut colonization and lower post-transplant mortality. In this study, using an expanded cohort, we evaluated whether our previously observed association is species-specific. We included allo-HCT recipients with 1 positive rectal swab or stool culture for iVRE between days -14 and +14 of transplant. To investigate whether iVRE modulate the gut microbiota, we performed agar diffusion assays. To investigate whether iVRE differ in their ability to activate the aryl hydrocarbon receptor, we analyzed iVRE genomes for enzymes in the shikimate and tryptophan pathways. Sixty six (23 E. casseliflavus and 43 E. gallinarum) of the 908 allograft recipients (2011–2017) met our inclusion criteria. Overall survival was significantly higher in patients with E. casseliflavus (91{\%} vs. 62{\%} at 3 years, P = 0.04). In multivariable analysis, E. casseliflavus gut colonization was significantly associated with reduced all-cause mortality (hazard ratio 0.20, 95{\%} confidence interval 0.04–0.91, P = 0.04). While agar assays were largely unremarkable, genome mining predicted that E. casseliflavus encodes a larger number of enzymes in the tryptophan metabolism pathway. In conclusion, E. casseliflavus gut colonization is associated with reduced post-HCT morality. Further research is needed to understand the mechanisms for this association.",
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AU - Barnes, Aaron M

AU - De For, Todd E

AU - Ferrieri, Patricia

AU - Young, Jo-Anne H

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AU - Weisdorf, Daniel J

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