Infectious Complications Are Associated With Alterations in the Gut Microbiome in Pediatric Patients With Acute Lymphoblastic Leukemia

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/28

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

30838178

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2019.00028

URI

Authors

Nearing JT, Connors J, Whitehouse S, Van Limbergen J, Macdonald T, Kulkarni K, Langille MGI

Journal

Frontiers in cellular and infection microbiology

Year

2019

Keywords:

cancer, clinical, genomics, infection, leukemia, metagenomics, microbiome

Acute lymphoblastic leukemia is the most common pediatric cancer. Fortunately, survival rates exceed 90%, however, infectious complications remain a significant issue that can cause reductions in the quality of life and prognosis of patients. Recently, numerous studies have linked shifts in the gut microbiome composition to infection events in various hematological malignances including acute lymphoblastic leukemia (ALL). These studies have been limited to observing broad taxonomic changes using 16S rRNA gene profiling, while missing possible differences within microbial functions encoded by individual species. In this study we present the first combined 16S rRNA gene and metagenomic shotgun sequencing study on the gut microbiome of an independent pediatric ALL cohort during treatment. In this study we found distinctive differences in alpha diversity and beta diversity in samples from patients with infectious complications in the first 6 months of therapy. We were also able to find specific species and functional pathways that were significantly different in relative abundance between samples that came from patients with infectious complications. Finally, machine learning models based on patient metadata and bacterial species were able to classify samples with high accuracy (84.09%), with bacterial species being the most important classifying features. This study strengthens our understanding of the association between infection and pediatric acute lymphoblastic leukemia treatment and warrants further investigation in the future.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/28

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Subjects

Location of subjects: Canada

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 lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia,Acute lymphoblastic leukemia

Group 0 name Corresponds to the control (unexposed) group for case-control studies: non-infectious complications (NIC)

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Infectious complications (IC) in the past 6 months of Acute Lymphoblastic Leukemia treatment

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: 9

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Prophylactic Septra which was prescribed ubiquitously to patients throughout the study, as per standard of care.

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

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: unchanged

Richness Number of species: decreased

Signature 1

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Curated date: 2021/01/10

Curator: William Lam

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Source: Figure 3, Supp. Figure 10-12

Description: Differential microbial abundance between patients who experienced infectious complications and those who did not

Abundance in Group 1: decreased abundance in Infectious complications (IC)

NCBI	Quality Control	Links
Bacteroidaceae
Bifidobacteriaceae
Eubacteriaceae
Methanobacteriota
Faecalibacterium prausnitzii
Oscillospiraceae
Prevotellaceae
Rikenellaceae
unclassified Bacteroidota
Bifidobacterium
Bacteroides
Prevotella
Alistipes
Dorea
Faecalibacterium

Revision editor(s): Claregrieve1, WikiWorks

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Curated date: 2021/01/10

Curator: William Lam

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Source: Figure 3a

Description: Differential microbial abundance between patients who experienced infectious complications and those who did not

Abundance in Group 1: increased abundance in Infectious complications (IC)

NCBI	Quality Control	Links
Achromobacter sp.
Agrobacterium
Agrobacterium tumefaciens
Alcaligenes
Brevundimonas diminuta
Brevundimonas
Bordetella
Caulobacteraceae
Rhizobiaceae
Alcaligenaceae
Burkholderiaceae
Pseudomonadota

Revision editor(s): Claregrieve1, WikiWorks