Cargando…

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

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 rat...

Descripción completa

Detalles Bibliográficos
Autores principales: Rajagopala, Seesandra V., Yooseph, Shibu, Harkins, Derek M., Moncera, Kelvin J., Zabokrtsky, Keri B., Torralba, Manolito G., Tovchigrechko, Andrey, Highlander, Sarah K., Pieper, Rembert, Sender, Leonard, Nelson, Karen E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986186/
https://www.ncbi.nlm.nih.gov/pubmed/27527070
http://dx.doi.org/10.1186/s12864-016-2965-y
_version_ 1782448162276900864
author Rajagopala, Seesandra V.
Yooseph, Shibu
Harkins, Derek M.
Moncera, Kelvin J.
Zabokrtsky, Keri B.
Torralba, Manolito G.
Tovchigrechko, Andrey
Highlander, Sarah K.
Pieper, Rembert
Sender, Leonard
Nelson, Karen E.
author_facet Rajagopala, Seesandra V.
Yooseph, Shibu
Harkins, Derek M.
Moncera, Kelvin J.
Zabokrtsky, Keri B.
Torralba, Manolito G.
Tovchigrechko, Andrey
Highlander, Sarah K.
Pieper, Rembert
Sender, Leonard
Nelson, Karen E.
author_sort Rajagopala, Seesandra V.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2965-y) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4986186
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-49861862016-08-17 Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis Rajagopala, Seesandra V. Yooseph, Shibu Harkins, Derek M. Moncera, Kelvin J. Zabokrtsky, Keri B. Torralba, Manolito G. Tovchigrechko, Andrey Highlander, Sarah K. Pieper, Rembert Sender, Leonard Nelson, Karen E. BMC Genomics Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2965-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-15 /pmc/articles/PMC4986186/ /pubmed/27527070 http://dx.doi.org/10.1186/s12864-016-2965-y Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rajagopala, Seesandra V.
Yooseph, Shibu
Harkins, Derek M.
Moncera, Kelvin J.
Zabokrtsky, Keri B.
Torralba, Manolito G.
Tovchigrechko, Andrey
Highlander, Sarah K.
Pieper, Rembert
Sender, Leonard
Nelson, Karen E.
Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
title Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
title_full Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
title_fullStr Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
title_full_unstemmed Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
title_short Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
title_sort gastrointestinal microbial populations can distinguish pediatric and adolescent acute lymphoblastic leukemia (all) at the time of disease diagnosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986186/
https://www.ncbi.nlm.nih.gov/pubmed/27527070
http://dx.doi.org/10.1186/s12864-016-2965-y
work_keys_str_mv AT rajagopalaseesandrav gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT yoosephshibu gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT harkinsderekm gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT moncerakelvinj gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT zabokrtskykerib gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT torralbamanolitog gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT tovchigrechkoandrey gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT highlandersarahk gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT pieperrembert gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT senderleonard gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis
AT nelsonkarene gastrointestinalmicrobialpopulationscandistinguishpediatricandadolescentacutelymphoblasticleukemiaallatthetimeofdiseasediagnosis