Dataset Information

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

ABSTRACT:

Background

The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed.

Methods

We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations.

Results

We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4 days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition.

Discussion

Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.

SUBMITTER: Elgarten CW

PROVIDER: S-EPMC8629955 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

Elgarten Caitlin W CW Tanes Ceylan C Lee Jung-Jin JJ Danziger-Isakov Lara A LA Grimley Michael S MS Green Michael M Michaels Marian G MG Barnum Jessie L JL Ardura Monica I MI Auletta Jeffery J JJ Blumenstock Jesse J Seif Alix E AE Bittinger Kyle L KL Fisher Brian T BT

Pediatric blood & cancer 20211028 1

<h4>Background</h4>The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed.<h4>Methods</h4>We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted ...[more]

PMID: 34709713

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Project description:BackgroundIncreasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients' immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly.ResultsIn two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state.ConclusionsWe identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.

Dataset Information

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

Background

Methods

Results

Discussion

Publications

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

Similar Datasets

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