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Microbiota Predict Infections and Acute Graft-Versus-Host Disease After Pediatric Allogeneic Hematopoietic Stem Cell
Elisa B Margolis1,2, Gabriela Maron Alfaro1,2, Yilun Sun3
1Department of Infectious Diseases, St Jude Children's Research Hospital.
Insights
Gut microbiota patterns predict infection risk in pediatric stem cell transplant patients. Specific bacterial ratios before and after transplant are linked to bacteremia, bacterial infections, and viral enterocolitis, offering potential biomarkers.
Area of Science:
- Microbiology
- Pediatric Hematology/Oncology
- Transplantation Science
Background:
- Infections remain a significant risk for pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients despite preventive measures.
- The gut microbiota's role in clinical outcomes is established in adults, prompting investigation in pediatric allo-HCT.
- This study aimed to identify specific gut microbiota patterns associated with infection risk in children undergoing allo-HCT.
Purpose of the Study:
- To evaluate gut microbiota signatures and their association with infection risk in pediatric allo-HCT recipients.
- To determine if adult-derived microbiota patterns predict infection risk in the pediatric population.
- To identify specific microbial ratios as potential biomarkers for infections and acute graft-versus-host disease (aGVHD) post-allo-HCT.
Main Methods:
- A prospective observational study involving 74 pediatric allo-HCT recipients.
- Fecal samples collected pre-conditioning and upon neutrophil recovery.
- Microbiome sequencing and Cox proportional hazards analysis to assess associations with infections and aGVHD.
Main Results:
- General microbiome disruption did not predict infection risk in pediatric allo-HCT, unlike in adults.
- Distinct microbial signatures were associated with specific infections and aGVHD.
- Pre-conditioning ratios of strict and facultative anaerobes predicted bacteremia risk (HR, 3.89).
- Post-neutrophil recovery ratios of oral to intestinal anaerobes predicted bacterial infections (HR, 1.81) and viral enterocolitis (HR, 1.96).
Conclusions:
- Microbiota signatures in pediatric allo-HCT are influenced by host-microbe-treatment interactions and can predict infection risk.
- Specific bacterial ratios show promise as predictive biomarkers for infections.
- Further multicenter validation is required to confirm the generalizability of these findings.
Background:
Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT.
Methods:
In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis.
Results:
Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96).
Conclusions:
Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.
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