Gut microbiota profiles of treatment-naïve adult acute myeloid leukemia patients with neutropenic fever during intensive chemotherapy

Study information

Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-7

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

33112882

DOI Digital object identifier for electronic documents.

https://doi.org/10.1371/journal.pone.0236460

URI

https://pubmed.ncbi.nlm.nih.gov/33112882/

Authors

Rattanathammethee T, Tuitemwong P, Thiennimitr P, Sarichai P, Na Pombejra S, Piriyakhuntorn P, Hantrakool S, Chai-Adisaksopha C, Rattarittamrong E, Tantiworawit A, Norasetthada L

Journal

PloS one

Year

2020

The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse. However, there are few reports of alterations of in adult acute myeloid leukemia (AML) patients. Stool samples of each treatment-naïve AML patient were collected the day before initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. No antimicrobial prophylaxis was in placed in all participants. Ten cases of AML patients (4 male and 6 female) were included with a median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes dominated during the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference +20.2; p < 0.0001) while Escherichia notably declined during the same period (mean difference -11.2; p = 0.0064). At the operational taxonomic unit (OTU) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTU of 203.1 vs. 131.7; p = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease during the febrile neutropenic period. Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow.

Experiment 1

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Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8

Curated date: 2023/03/13

Curator: Cyberian

Revision editor(s): Chloe, Cyberian, Aiyshaaaa, Folakunmi

Subjects

Location of subjects: Thailand

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: Acute myeloid leukemia acute granulocytic leukemia,acute myeloblastic leukemia,acute myelocytic leukemia,acute myelogenous leukemia,acute myelogenous leukemias,acute myeloid leukemia,acute myeloid leukemia (AML),acute non lymphoblastic leukemia,acute Nonlymphocytic leukemia,acute nonlymphocytic leukemia,AML,AML - acute myeloid leukemia,ANLL,hematopoeitic - acute Myleogenous leukemia (AML),leukemia, acute myelogenous,leukemia, acute myeloid,leukemia, acute myeloid, susceptibility to,leukemia, myelocytic, acute,myeloid leukemia, acute,Acute myeloid leukemia

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

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: patients with neutropenic fever during intensive chemotherapy

Group 0 sample size Number of subjects in the control (unexposed) group: 10

Group 1 sample size Number of subjects in the case (exposed) group: 10

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months.

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-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: ANOVA

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

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

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Folakunmi on 2024-2-12

Curated date: 2023/03/14

Curator: Cyberian

Revision editor(s): Chloe, Cyberian, Aiyshaaaa, Folakunmi

Source: S1 table.

Description: The taxa that increased in relative abundance from pretreatment to febrile neutropenia.

Abundance in Group 1: increased abundance in Febrile neutropenia

NCBI	Quality Control	Links
Enterococcus

Revision editor(s): Chloe, Cyberian, Aiyshaaaa, Folakunmi

Signature 2

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Reviewed Marked as Reviewed by Folakunmi on 2024-2-12

Curated date: 2023/03/14

Curator: Cyberian

Revision editor(s): Cyberian, Chloe, Folakunmi

Source: S1 table.

Description: Taxa that decreased in relative abundance from pretreatment to febrile neutropenia

Abundance in Group 1: decreased abundance in Febrile neutropenia

NCBI	Quality Control	Links
Escherichia

Revision editor(s): Cyberian, Chloe, Folakunmi

Experiment 2

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Reviewed Marked as Reviewed by Folakunmi on 2024-2-13

Curated date: 2023/03/13

Curator: Cyberian

Revision editor(s): Cyberian, Aiyshaaaa, Folakunmi

Differences from previous experiment shown

Subjects

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

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: After initiation of induction chemotherapy

Lab analysis

Statistical Analysis

Alpha Diversity

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

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

Richness Number of species: unchanged

Experiment 3

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Reviewed Marked as Reviewed by Folakunmi on 2024-2-13

Curated date: 2023/03/25

Curator: Cyberian

Revision editor(s): Cyberian, Aiyshaaaa, Folakunmi

Differences from previous experiment shown

Subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: After initiation of induction chemotherapy treatment