Loss of microbiota-derived protective metabolites after neutropenic fever

Armin Rashidi, Maryam Ebadi, Tauseef Ur Rehman, Heba Elhusseini, Hossam Halaweish, Shernan G. Holtan, Sivapriya Ramamoorthy, Daniel J Weisdorf, Alexander Khoruts, Christopher Staley

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Neutropenic fever (NF) is a common complication of chemotherapy in patients with cancer which often prolongs hospitalization and worsens the quality of life. Although an empiric antimicrobial approach is used to prevent and treat NF, a clear etiology cannot be found in most cases. Emerging data suggest an altered microbiota-host crosstalk leading to NF. We profiled the serum metabolome and gut microbiome in longitudinal samples before and after NF in patients with acute myeloid leukemia, a prototype setting with a high incidence of NF. We identified a circulating metabolomic shift after NF, with a minimal signature containing 18 metabolites, 13 of which were associated with the gut microbiota. Among these metabolites were markers of intestinal epithelial health and bacterial metabolites of dietary tryptophan with known anti-inflammatory and gut-protective effects. The level of these metabolites decreased after NF, in parallel with biologically consistent changes in the abundance of mucolytic and butyrogenic bacteria with known effects on the intestinal epithelium. Together, our findings indicate a metabolomic shift with NF which is primarily characterized by a loss of microbiota-derived protective metabolites rather than an increase in detrimental metabolites. This analysis suggests that the current antimicrobial approach to NF may need a revision to protect the commensal microbiota.

Original languageEnglish (US)
Article number6244
JournalScientific reports
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences grants KL2TR002492 and UL1TR002494, and in part by NIH P30 CA77598 utilizing the Translational Therapy Laboratory Shared Resource of the Masonic Cancer Center, University of Minnesota. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2022, The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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