Abstract
Background
Neutropenic fever (NF) occurs in >70% of hematopoietic cell transplantation (HCT) recipients, without a documented etiology in most cases. Antibiotics used to prevent and treat NF disrupt the gut microbiota; these disruptions predict higher post-transplant mortality. 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, 1,278 patients) to find pairs with (cases) vs. without (controls) NF on the same day relative to transplantation and with a stool sample on the previous day. 179 such pairs were matched in 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 had a lower abundance of
Blautia than their m atched controls on the same day post-transplant, 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 acute leukemia patients 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 where
Blautia protects against NF by improving intestinal health. Therapeutic restoration of
Blautia may help prevent NF, thus reducing antibiotic exposures and transplant-related mortality.
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