Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study

Study information

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

31065565

DOI Digital object identifier for electronic documents.

10.1093/ofid/ofz173

URI

Authors

Galloway-Peña JR, Peterson CB, Malik F, Sahasrabhojane PV, Shah DP, Brumlow CE, Carlin LG, Chemaly RF, Im JS, Rondon G, Felix E, Veillon L, Lorenzi PL, Alousi AM, Jenq RR, Kontoyiannis DP, Shpall EJ, Shelburne SA, Okhuysen PC

Journal

Open forum infectious diseases

Year

2019

Keywords:

butyrate, graft-vs-host disease (GVHD), hematopoietic stem cell transplant (HSCT), indole, microbiome

Background: Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers. Methods: Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry. Results: Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03). Conclusions: Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.

Experiment 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Peace Sandy

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Response to allogeneic hematopoietic stem cell transplant Response to allogeneic hematopoietic stem cell transplant,response to allogeneic hematopoietic stem cell transplant

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy volunteers

Group 1 name Corresponds to the case (exposed) group for case-control studies: hematopoietic stem cell transplant recipients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: patients undergoing T cell repleted allogeneic hematopoietic stem cell transplantation

Group 0 sample size Number of subjects in the control (unexposed) group: 18

Group 1 sample size Number of subjects in the case (exposed) group: 50

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Text, Figure 1

Description: Clinical and Microbime Predictors of Acute GastroIntestinal Graft-vs- Host Disease

Abundance in Group 1: increased abundance in hematopoietic stem cell transplant recipients

NCBI	Quality Control	Links
Enterococcus

Revision editor(s): WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Text, Figure 1

Description: Clinical and Microbime Predictors of Acute GastroIntestinal Graft-vs- Host Disease

Abundance in Group 1: decreased abundance in hematopoietic stem cell transplant recipients

NCBI	Quality Control	Links
Pseudobutyrivibrio
Subdoligranulum

Revision editor(s): WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: low fecal butyrate levels

Group 1 name Corresponds to the case (exposed) group for case-control studies: high fecal butyrate levels

Group 0 sample size Number of subjects in the control (unexposed) group: 50

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified

Statistical test: LEfSe

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 4

Signature 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Text, Figure 3, Supplemental figure 2

Description: Differences in fecal metabolites among hemapoietic stem cell transplant (HSCT) recipients at baseline

Abundance in Group 1: increased abundance in high fecal butyrate levels

NCBI	Quality Control	Links
Clostridia
Eubacteriales
Lachnospiraceae
Eggerthella
Oscillospiraceae
Ruminiclostridium
Lachnoclostridium
Blautia
Erysipelotrichia
Erysipelotrichales
Erysipelotrichaceae
Pseudobutyrivibrio
Thomasclavelia