Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-7

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

30988420

DOI Digital object identifier for electronic documents.

10.1038/s41598-019-42652-6

URI

Authors

Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Holtan SG, Rehman TU, Wasko J, Weisdorf DJ, Dunny G, Khoruts A, Staley C

Journal

Scientific reports

Year

2019

Acute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo "repeat therapy" (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. To test this hypothesis, we analyzed the bacterial microbiome profiles of thrice-weekly stool samples from 20 intensively treated AL patients (first induction: 13, repeat therapy: 7) by 16S rRNA sequencing. In mixed-effects modeling, repeat therapy was a significant predictor of Enterococcus expansion (P = 0.006), independently of antibiotic exposure, disease type, feeding mode, and week of chemotherapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-7

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

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: Leukemia blood (leukemia),leukemia,leukemia (disease),leukemia, disease,leukemia, malignant,leukemias,leukemias, general,Leukemia

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: induction

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: acute leukemia patients undergoing chemotherapy

Group 0 sample size Number of subjects in the control (unexposed) group: 7

Group 1 sample size Number of subjects in the case (exposed) group: 13

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: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.01

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

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

Alpha Diversity

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

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-7

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks, Claregrieve1

Source: Figure 2b

Description: Composition of microbial communities during induction and repeat therapy in leukemia patients

Abundance in Group 1: increased abundance in induction

NCBI	Quality Control	Links
Bacteroides
Faecalibacterium
Oscillibacter
Parabacteroides
Ruminococcus

Revision editor(s): WikiWorks, Claregrieve1

Signature 2

Edit History Delete

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Your review change was submitted

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-7

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks, Claregrieve1

Source: Figure 2b

Description: Composition of microbial communities during induction and repeat therapy in leukemia patients

Abundance in Group 1: decreased abundance in induction

NCBI	Quality Control	Links
Actinomyces
Eggerthella
Enterococcus
Faecalicoccus
Lactobacillus
Subdoligranulum
Veillonella

Revision editor(s): WikiWorks, Claregrieve1