Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia: The impact of the gut microbiota.
Adolescent
Bacteria
/ classification
Case-Control Studies
Child
Child, Preschool
DNA, Bacterial
/ genetics
DNA, Ribosomal
/ genetics
Feces
/ microbiology
Female
Gastrointestinal Microbiome
/ drug effects
Humans
Induction Chemotherapy
/ adverse effects
Infant
Male
Mucositis
/ chemically induced
Phylogeny
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Prospective Studies
RNA, Ribosomal, 16S
/ genetics
Sequence Analysis, DNA
/ methods
Siblings
C-reactive protein
acute lymphoblastic leukemia
citrulline
gastrointestinal toxicity
microbiota
mucositis
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
10
09
2019
revised:
19
01
2020
accepted:
04
02
2020
pubmed:
3
3
2020
medline:
10
4
2021
entrez:
3
3
2020
Statut:
ppublish
Résumé
Intestinal mucositis is a common side effect of chemotherapy leading to diarrhea, abdominal pain and increased risk of infections. The intestinal microbiota has been recognized as a key regulator of mucosal immune responses. Therefore, we hypothesized that intestinal microbial changes would be associated with enterocyte loss and systemic inflammation during induction treatment for childhood acute lymphoblastic leukemia (ALL). We prospectively included 51 children newly-diagnosed with ALL treated in Denmark in 2015-2018. Plasma C-reactive protein (CRP), plasma citrulline (marker of functional enterocytes mass) measurements and fecal samplings were performed on treatment Days 1, 8, 15, 22 and 29. Moreover, intestinal mucositis was scored by a trained nurse/physician. Fecal samples in patients and 19 healthy siblings were analyzed by 16S rRNA gene sequencing (V3-V4 region). Bacterial alpha diversity was lower in patients compared to siblings. It decreased from Day 1 to Days 8-22 and increased on Day 29. Shannon alpha diversity index was correlated with CRP on Days 15-29 (rho = -0.33-0.49; p < 0.05) and with citrulline on Days 15 and 29 (although with p values <0.06, rho = 0.32-0.34). The abundance of unclassified Enterococcus species (spp.) was correlated with CRP on Days 22-29 (rho = 0.42-0.49; p < 0.009), while the abundance of unclassified Lachnospiraceae spp. was correlated with citrulline on days 8-15 (rho = 0.48-0.62, p < 0.001). Systemic inflammation, enterocyte loss and relative abundance of unclassified Enterococcus spp. reached a peak around Day 15. In conclusion, specific changes in the microbiota were associated with the severity of enterocyte loss and systemic inflammation during chemotherapy.
Substances chimiques
DNA, Bacterial
0
DNA, Ribosomal
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1953-1962Informations de copyright
© 2020 UICC.
Références
Pui C-H, Yang JJ, Hunger SP, et al. Childhood acute lymphoblastic leukemia: Progress through collaboration. J Clin Oncol 2015;33:2938-49.
Sonis ST. The pathobiology of mucositis. Nat Rev Cancer 2004;4:277-84.
Lalla RV, Bowen J, Barasch A, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453-61.
de Pietri S, Nielsen BN, Ifversen M, et al. Morphine consumption is associated with systemic inflammation in children undergoing allogeneic hematopoietic stem cell transplantation. Immunopharmacol Immunotoxicol 2019;41:285-91.
van der Velden WJFM, Herbers AHE, Netea MG, et al. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis. Br J Haematol 2014;167:441-52.
Kornblit B, Müller K. Sensing danger: toll-like receptors and outcome in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2017;52:499-505.
Schots R, Kaufman L, van Riet I, et al. Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation. Leukemia 2003;17:1150-6.
Fragkos KC, Forbes A. Citrulline as a marker of intestinal function and absorption in clinical settings: a systematic review and meta-analysis. United Eur Gastroenterol J 2018;6:181-91.
Touchefeu Y, Montassier E, Nieman K, et al. Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis-current evidence and potential clinical applications. Aliment Pharmacol Ther 2014;40:409-21.
Qin H-L, Shen T-Y, Gao Z-G, et al. Effect of lactobacillus on the gut microflora and barrier function of the rats with abdominal infection. World J Gastroenterol 2005;11:2591-6.
Hamer HM, Jonkers D, Venema K, et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 2008;27:104-19.
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229-41.
Montassier E, Gastinne T, Vangay P, et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther 2015;42:515-28.
Lin XB, Dieleman LA, Ketabi A, et al. Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats. PLoS One 2012;7:e39764.
Toft N, Birgens H, Abrahamsson J, et al. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol. Eur J Haematol 2013;90:404-12.
Chaimbault P, Petritis K, Elfakir C, et al. Determination of 20 underivatized proteinic amino acids by ion-pairing chromatography and pneumatically assisted electrospray mass spectrometry. J Chromatogr A 1999;855:191-202.
Illumina®. 16S Metagenomic Sequencing Library Preparation. Part #15044223 Rev B. Available from https://support.illumina.com/documents/documentation/chemistry_documentation/16s/16s-metagenomic-library-prep-guide-15044223-b.pdf. 2013;1-28.
Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J 2011;17:10-2.
Callahan BJ, McMurdie PJ, Rosen MJ, et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods 2016;13:581-3.
Callahan B. Silva taxonomic training data formatted for DADA2 (Silva version 132). Zenodo. 2018.
Davis NM, Proctor DM, Holmes SP, et al. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 2018;6:226.
Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010;7:335-6.
Rathe M, De Pietri S, Wehner PS, et al. Bovine colostrum against chemotherapy-induced gastrointestinal toxicity in children with acute lymphoblastic leukemia: a randomized, double-blind, placebo-controlled trial. J Parenter Enteral Nutr 2019;44:337-47.
Rajagopala SV, Yooseph S, Harkins DM, et al. Gastrointestinal microbial populations can distinguish pediatric and adolescent acute lymphoblastic leukemia (ALL) at the time of disease diagnosis. BMC Genomics 2016;17:635.
Bai L, Zhou P, Li D, et al. Changes in the gastrointestinal microbiota of children with acute lymphoblastic leukaemia and its association with antibiotics in the short term. J Med Microbiol 2017;66:1297-307.
Ye H, Adane B, Khan N, et al. Subversion of systemic glucose metabolism as a mechanism to support the growth of leukemia cells. Cancer Cell 2018;34:659-673.e6.
Taur Y, Xavier JB, Lipuma L, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:905-14.
Holler E, Butzhammer P, Schmid K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014;20:640-5.
Ingham AC, Kielsen K, Cilieborg MS, et al. Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation. Microbiome 2019;7:131.
Galloway-Peña JR, Smith DP, Sahasrabhojane P, et al. The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia. Cancer 2016;122:2186-96.
Hakim H, Dallas R, Wolf J, et al. Gut microbiome composition predicts infection risk during chemotherapy in children with acute lymphoblastic leukemia. Clin Infect Dis 2018;67:541-8.
Forsgård RA, Marrachelli VG, Katri K, et al. Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats. Cancer Chemother Pharmacol 2017;80:317-32.
Wu C-H, Ko J-L, Liao J-M, et al. D-methionine alleviates cisplatin-induced mucositis by restoring the gut microbiota structure and improving intestinal inflammation. Ther Adv Med Oncol 2019;11:175883591882102.
Wang A, Ling Z, Yang Z, et al. Gut microbial Dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One 2015;10:e0126312.
Jenq RR, Ubeda C, Taur Y, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med 2012;209:903-11.
Kolho KL, Korpela K, Jaakkola T, et al. Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol 2015;110:921-30.
Bach Knudsen K, Laerke H, Hedemann M, et al. Impact of diet-modulated butyrate production on intestinal barrier function and inflammation. Nutrients 2018;10:1499.
Ferreira TM, Leonel AJ, Melo MA, et al. Oral supplementation of butyrate reduces mucositis and intestinal permeability associated with 5-fluorouracil administration. Lipids 2012;47:669-78.
Hiippala K, Kainulainen V, Kalliomäki M, et al. Mucosal prevalence and interactions with the epithelium indicate commensalism of Sutterella spp. Front Microbiol 2016;7:1706.
Shallis RM, Terry CM, Lim SH. Changes in intestinal microbiota and their effects on allogeneic stem cell transplantation. Am J Hematol 2018;93:122-8.
Arias CA, Murray BE. The rise of the enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 2012;10:266-78.
Phillips RS, Sung L, Ammann RA, et al. Predicting microbiologically defined infection in febrile neutropenic episodes in children: global individual participant data multivariable meta-analysis. Br J Cancer 2016;114:623-30.
van Vliet MJ, Tissing WJE, Dun CAJ, et al. Chemotherapy treatment in pediatric patients with acute myeloid leukemia receiving antimicrobial prophylaxis leads to a relative increase of colonization with potentially pathogenic bacteria in the gut. Clin Infect Dis 2009;49:262-70.
Steck N, Hoffmann M, Sava IG, et al. Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 2011;141:959-71.
Kim SO, Sheikh HI, Ha S-D, et al. G-CSF-mediated inhibition of JNK is a key mechanism for lactobacillus rhamnosus-induced suppression of TNF production in macrophages. Cell Microbiol 2006;8:1958-71.
Fite A, Macfarlane S, Furrie E, et al. Longitudinal analyses of gut mucosal microbiotas in ulcerative colitis in relation to patient age and disease severity and duration. J Clin Microbiol 2013;51:849-56.
Nycz BT, Dominguez SR, Friedman D, et al. Evaluation of bloodstream infections, Clostridium difficile infections, and gut microbiota in pediatric oncology patients. PLoS One 2018;13:e0191232.
Montassier E, Al-Ghalith GA, Ward T, et al. Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection. Genome Med 2016;8:49.
Wardill HR, Tissing WJE. Determining risk of severe gastrointestinal toxicity based on pretreatment gut microbial community in patients receiving cancer treatment: a new predictive strategy in the quest for personalized cancer medicine. Curr Opin Support Palliat Care 2017;11:125-32.
Ciorba MA, Hallemeier CL, Stenson WF, et al. Probiotics to prevent gastrointestinal toxicity from cancer therapy: an interpretive review and call to action. Curr Opin Support Palliat Care 2015;9:157-62.