Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs Host Disease After Hematopoietic Cell Transplantation
Open accessAbstract
BACKGROUND: Graft-versus-host disease (GVHD) is common after allogeneic hematopoietic cell transplantation (HCT). Risk for death from GVHD has been associated with low bacterial diversity in the stool microbiota early after transplant; however, the specific species associated with GVHD risk remain poorly defined. METHODS: We prospectively collected serial weekly stool samples from 66 patients who underwent HCT, starting pre-transplantation and continuing weekly until 100 days post-transplant, a total of 694 observations in HCT recipients. We used 16S rRNA gene polymerase chain reaction with degenerate primers, followed by high-throughput sequencing to assess the relative abundance of sequence reads from bacterial taxa in stool samples over time. RESULTS: The gut microbiota was highly dynamic in HCT recipients, with loss and appearance of taxa common on short time scales. As in prior studies, GVHD was associated with lower alpha diversity of the stool microbiota. At neutrophil recovery post-HCT, the presence of oral Actinobacteria and oral Firmicutes in stool was positively correlated with subsequent GVHD; Lachnospiraceae were negatively correlated. A gradient of bacterial species (difference of the sum of the relative abundance of positive correlates minus the sum of the relative abundance of negative correlates) was most predictive (receiver operator characteristic area under the curve of 0.83) of subsequent severe acute GVHD. CONCLUSIONS: The stool microbiota around the time of neutrophil recovery post-HCT is predictive of subsequent development of severe acute GVHD in this study.
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Allogeneic HCT patients show microbiota disruption, including overgrowth of potential pathogens and reduced alpha diversity.
“We and others have reported that patients undergoing allogeneic hematopoietic-cell transplantation have microbiota disruption that is characterized by expansions of potentially pathogenic bacteria and loss of alpha diversity — a variable that reflects the number of unique bacterial taxa present and their relative frequencies.2–5”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [4]
Single-center studies have linked post-HCT intestinal microbiota features to relapse, GVHD, infection, organ toxicity, and overall survival.
“Each of these outcomes, as well as overall survival, has been associated in single-center studies with features of the intestinal microbiota in the period after hematopoietic-cell transplantation.2–4,8–15”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [4]
This multicenter study extends earlier findings from smaller single-center cohorts.
“The results of this international study extend previous observations that have been made in smaller, single-center cohorts.3,4,8,36”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [4]
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Respiratory Bacteria Stabilize and Promote Airborne Transmission of Influenza A Virus
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Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease
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Self-citationImpact of Topical Interventions on the Vaginal Microbiota and Metabolome in Postmenopausal Women
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Self-citationFecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease
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Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome
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How I Prevent Viral Reactivation in High-risk Patients
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The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease
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Biomarkers for acute and chronic graft versus host disease: state of the art
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Complex interactions of cellular players in chronic Graft-versus-Host Disease
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Controversies and expectations for the prevention of GVHD: A biological and clinical perspective
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Vaginal Microbiota and Mucosal Immune Markers in Women With Vulvovaginal Discomfort
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Self-citationMicrobiome Anomalies in Allogeneic Hematopoietic Cell Transplantation
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The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation
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Association Between Vaginal Bacterial Microbiota and Vaginal Yeast Colonization
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Self-citationOpportunities and Challenges for Gut Microbiota in Acute Leukemia
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Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease
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How I treat febrile neutropenia
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Molecular Diagnostic Advances in Transplant Infectious Diseases
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- Authors
- Golob, J. L., Pergam, S. A., Srinivasan, S., Fiedler, T. L., Liu, C., Garcia, K., Mielcarek, M., Ko, D., Aker, S., Marquis, S., Loeffelholz, T., Plantinga, A., Wu, M. C., Celustka, K., Morrison, A., Woodfield, M., & Fredricks, D. N.
- Affiliations
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Fredricks, David N
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08-18
- Volume
- 65
- Issue
- 12
- Pages
- 1984-1991
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC5850019
- OpenAlex
- W2750411590
- Cited by
- 201
- References
- 42
- Citations by year
- 2026: 9 · 2025: 25 · 2024: 19 · 2023: 29 · 2022: 29 · 2021: 29 · 2020: 33 · 2019: 19 · 2018: 9
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Clinical Infectious Diseases (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI134808, T32AI118690, T32AI007044)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- graft-versus-host disease, gut microbiota, hematopoietic stem cell transplantation, neutrophil recovery, bacterial diversity, actinobacteria, Firmicutes, Lachnospiraceae
- MeSH terms
- Bacillota, Gastrointestinal Microbiome, Adult, Aged, Bacteria, Feces, Female, Graft vs Host Disease, Humans, Male, Middle Aged, Neutrophils, Prospective Studies, RNA, Ribosomal, 16S, Polymerase Chain Reaction, Hematopoietic Stem Cell Transplantation, Actinobacteria, High-Throughput Nucleotide Sequencing
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