Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/24

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

27527070

DOI Digital object identifier for electronic documents.

10.1186/s12864-016-2965-y

URI

Authors

Rajagopala SV, Yooseph S, Harkins DM, Moncera KJ, Zabokrtsky KB, Torralba MG, Tovchigrechko A, Highlander SK, Pieper R, Sender L, Nelson KE

Journal

BMC genomics

Year

2016

Keywords:

16S rRNA gene sequencing, Gastrointestinal microbiota, Pediatric leukemia, Ribosomal RNA, rRNA

BACKGROUND: An estimated 15,000 children and adolescents under the age of 19 years are diagnosed with leukemia, lymphoma and other tumors in the USA every year. All children and adolescent acute leukemia patients will undergo chemotherapy as part of their treatment regimen. Fortunately, survival rates for most pediatric cancers have improved at a remarkable pace over the past three decades, and the overall survival rate is greater than 90 % today. However, significant differences in survival rate have been found in different age groups (94 % in 1-9.99 years, 82 % in ≥10 years and 76 % in ≥15 years). ALL accounts for about three out of four cases of childhood leukemia. Intensive chemotherapy treatment coupled with prophylactic or therapeutic antibiotic use could potentially have a long-term effect on the resident gastrointestinal (GI) microbiome. The composition of GI microbiome and its changes upon chemotherapy in pediatric and adolescent leukemia patients is poorly understood. In this study, using 16S rRNA marker gene sequences we profile the GI microbial communities of pediatric and adolescent acute leukemia patients before and after chemotherapy treatment and compare with the microbiota of their healthy siblings. RESULTS: Our study cohort consisted of 51 participants, made up of matched pediatric and adolescent patients with ALL and a healthy sibling. We elucidated and compared the GI microbiota profiles of patients and their healthy sibling controls via analysis of 16S rRNA gene sequencing data. We assessed the GI microbiota composition in pediatric and adolescent patients with ALL during the course of chemotherapy by comparing stool samples taken before chemotherapy with stool samples collected at varying time points during the chemotherapeutic treatment. The microbiota profiles of both patients and control sibling groups are dominated by members of Bacteroides, Prevotella, and Faecalibacterium. At the genus level, both groups share many taxa in common, but the microbiota diversity of the patient group is significantly lower than that of the control group. It was possible to distinguish between the patient and control groups based on their microbiota profiles. The top taxa include Anaerostipes, Coprococcus, Roseburia, and Ruminococcus2 with relatively higher abundance in the control group. The observed microbiota changes are likely the result of several factors including a direct influence of therapeutic compounds on the gut flora and an indirect effect of chemotherapy on the immune system, which, in turn, affects the microbiota. CONCLUSIONS: This study provides significant information on GI microbiota populations in immunocompromised children and opens up the potential for developing novel diagnostics based on stool tests and therapies to improve the dysbiotic condition of the microbiota at the time of diagnosis and in the earliest stages of chemotherapy.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/24

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks

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: 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: healthy sibling control

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with pediatric and adolescent Acute Lymphoblastic Leukemia at time of disease diagnosis

Group 0 sample size Number of subjects in the control (unexposed) group: 23

Group 1 sample size Number of subjects in the case (exposed) group: 28

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V3

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

Statistical Analysis

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)?: No

Alpha Diversity

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

Signature 1

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Curated date: 2021/01/10

Curator: William Lam

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Source: Text

Description: Mean microbial taxon abundances in Acute Lymphoblastic Leukemia Patient and Control groups (prior to chemotherapy treatment- visit 1)

Abundance in Group 1: increased abundance in adolescent ALL patient

NCBI	Quality Control	Links
Bacteroides

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/24

Curated date: 2021/01/10

Curator: William Lam

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Source: Text

Description: Mean microbial taxon abundances in Acute Lymphoblastic Leukemia Patient and Control groups (prior to chemotherapy treatment- visit 1)

Abundance in Group 1: decreased abundance in adolescent ALL patient

NCBI	Quality Control	Links
Roseburia
Lachnospiraceae

Revision editor(s): Claregrieve1, WikiWorks