Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy

Study information

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study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

32093640

DOI Digital object identifier for electronic documents.

10.1186/s12885-020-6654-5

URI Uniform resource identifier for web resources.

Authors

Chua LL, Rajasuriar R, Lim YAL, Woo YL, Loke P, Ariffin H

Journal

BMC cancer

Year

2020

BACKGROUND: Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy. METHODOLOGY: We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy. RESULTS: Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health. CONCLUSION: Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

Experiment 1

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Curated date: 2021/01/10

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Subjects

Location of subjects

Malaysia

Host species Species from which microbiome was sampled (if applicable)

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

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

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

healthy control

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

Acute Lymphoblastic Leukemia diagnosis and Pre- Chemotherapy treatment

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

children (ages 2-6 years old) diagnosed with and treated for Acute Lymphoblastic Leukemia

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

7

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

Statistical test

DESeq2

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

0.1

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

Yes

Matched on Factors on which subjects have been matched on in a case-control study

Matched on: "Age" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Age, ethnic group

Signature 1

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Curated date: 2021/01/10

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Source: Figure 3a

Description: Differentially abundant bacteria were identified between Acute Lymphoblastic Leukemia (ALL) patients pre-chemotherapy and healthy controls

Abundance in Group 1: increased abundance in Acute Lymphoblastic Leukemia diagnosis and Pre- Chemotherapy treatment

NCBI	Links
Bacteroides
Bacteroides uniformis
Bacteroides fragilis

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Signature 2

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Source: Figure 3a

Description: Differentially abundant bacteria were identified between Acute Lymphoblastic Leukemia (ALL) patients pre-chemotherapy and healthy controls

Abundance in Group 1: decreased abundance in Acute Lymphoblastic Leukemia diagnosis and Pre- Chemotherapy treatment

NCBI	Links
Campylobacter
Veillonellaceae
Corynebacterium
Bifidobacterium
Atopobium
Peptoniphilus ⚠
Staphylococcus
Prevotella
Anaerococcus ⚠
Porphyromonas

Revision editor(s): WikiWorks

Signature 3

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Curated date: 2021/01/10

Curator: William Lam

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Source: Figure 3b

Description: Differentially abundant bacteria were identified between Acute Lymphoblastic Leukemia (ALL) patients post-chemotherapy and healthy controls

Abundance in Group 1: increased abundance in Acute Lymphoblastic Leukemia diagnosis and Pre- Chemotherapy treatment

NCBI	Links
Bifidobacterium

Revision editor(s): WikiWorks

Signature 4

EditHistoryDelete

Mark reviewed

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Needs review

Curated date: 2021/01/10

Curator: William Lam

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Source: Figure 3b

Description: Differentially abundant bacteria were identified between Acute Lymphoblastic Leukemia (ALL) patients post-chemotherapy and healthy controls

Abundance in Group 1: decreased abundance in Acute Lymphoblastic Leukemia diagnosis and Pre- Chemotherapy treatment

NCBI	Links
Atopobium
Bacteroides
Prevotella
Fusobacterium
Corynebacterium

Revision editor(s): WikiWorks