Protective Effect of Intestinal Blautia Against Neutropenic Fever in Allogeneic Transplant Recipients

Armin Rashidi, Jonathan U. Peled, Maryam Ebadi, Tauseef Ur Rehman, Heba Elhusseini, Lee Ann T. Marcello, Hossam Halaweish, Thomas J Kaiser-Powers, Shernan G. Holtan, Alexander Khoruts, Daniel J Weisdorf, Christopher Staley

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND: Neutropenic fever (NF) occurs in >70% of hematopoietic cell transplant (HCT) recipients, without a documented cause in most cases. Antibiotics used to prevent and treat NF disrupt the gut microbiota; these disruptions predict a higher posttransplantation mortality rate. We hypothesized that specific features in the gut microbial community may mediate the risk of NF. METHODS: We searched a large gut microbiota database in allogeneic HCT recipients (12 546 stool samples; 1278 patients) to find pairs with NF (cases) versus without NF (controls) on the same day relative to transplantation and with a stool sample on the previous day. A total of 179 such pairs were matched as to the underlying disease and graft source. Several other important clinical variables were similar between the groups. RESULTS: The gut microbiota of cases on the day before NF occurrence had a lower abundance of Blautia than their matched controls on the same day after transplantation, suggesting a protective role for Blautia. Microbiota network analysis did not find any differences in community structure between the groups, suggesting a single-taxon effect. To identify putative mechanisms, we searched a gut microbiome and serum metabolome database of patients with acute leukemia receiving chemotherapy and identified 139 serum samples collected within 24 hours after a stool sample from the same patient. Greater Blautia abundances predicted higher levels of next-day citrulline, a biomarker of total enterocyte mass. CONCLUSIONS: These findings support a model in which Blautia protects against NF by improving intestinal health. Therapeutic restoration of Blautia may help prevent NF, thus reducing antibiotic exposures and transplantation-related deaths.

Original languageEnglish (US)
Pages (from-to)1912-1920
Number of pages9
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume75
Issue number11
DOIs
StatePublished - Nov 30 2022

Bibliographical note

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Keywords

  • Blautia
  • hematopoietic cell transplantation
  • metabolomics
  • microbiota
  • neutropenic fever

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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