Gut dysbiosis during antileukemia chemotherapy versus allogeneic hematopoietic cell transplantation.
dysbiosis
leukemia
microbiota
transplantation
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
25
05
2019
revised:
30
09
2019
accepted:
19
10
2019
pubmed:
25
12
2019
medline:
6
11
2020
entrez:
25
12
2019
Statut:
ppublish
Résumé
In the field of malignant hematology, most microbiome studies have focused on recipients of allogeneic hematopoietic cell transplantation (allo-HCT). As a result, this population has remained the primary target for novel microbiota therapeutics. Because the types of insults to the microbiome are similar during hematopoietic cell transplantation and intensive antileukemia therapy, this study evaluated whether the dysbiosis states are similar in the 2 settings. This study compared gut microbiota assemblages and community domination states in 2 cohorts of patients: patients with intensively treated acute leukemia (AL) and allo-HCT recipients. 16S ribosomal RNA gene profiling of thrice weekly stool samples was performed. Linear discriminant analysis effect size was used to determine differentially abundant taxa in groups of interest, and mixed modes were used to determine the predictors of microbiome states. Microbiome changes in both cohorts were characterized by a marked loss of diversity and domination of low-diversity communities by Enterococcus. In the AL cohort, the relative abundance of Lactobacillus was also inversely correlated with diversity. Communities dominated by these genera were compositionally different. Similarities in microbiota assemblages between the 2 cohorts support a broader scope for microbiota-directed therapeutics than previously considered, whereas specific differences suggest a personalized aspect to such therapeutics with the possibility of a differential response.
Sections du résumé
BACKGROUND
In the field of malignant hematology, most microbiome studies have focused on recipients of allogeneic hematopoietic cell transplantation (allo-HCT). As a result, this population has remained the primary target for novel microbiota therapeutics. Because the types of insults to the microbiome are similar during hematopoietic cell transplantation and intensive antileukemia therapy, this study evaluated whether the dysbiosis states are similar in the 2 settings.
METHODS
This study compared gut microbiota assemblages and community domination states in 2 cohorts of patients: patients with intensively treated acute leukemia (AL) and allo-HCT recipients. 16S ribosomal RNA gene profiling of thrice weekly stool samples was performed. Linear discriminant analysis effect size was used to determine differentially abundant taxa in groups of interest, and mixed modes were used to determine the predictors of microbiome states.
RESULTS
Microbiome changes in both cohorts were characterized by a marked loss of diversity and domination of low-diversity communities by Enterococcus. In the AL cohort, the relative abundance of Lactobacillus was also inversely correlated with diversity. Communities dominated by these genera were compositionally different.
CONCLUSIONS
Similarities in microbiota assemblages between the 2 cohorts support a broader scope for microbiota-directed therapeutics than previously considered, whereas specific differences suggest a personalized aspect to such therapeutics with the possibility of a differential response.
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1434-1447Informations de copyright
© 2019 American Cancer Society.
Références
Buffie CG, Pamer EG. Microbiota-mediated colonization resistance against intestinal pathogens. Nat Rev Immunol. 2013;13:790-801. doi:10.1038/nri3535
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229-241. doi:10.1016/j.cell.2004.07.002
Swimm A, Giver CR, DeFilipp Z, et al. Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease. Blood. 2018;132:2506-2519. doi:10.1182/blood-2018-03-838193
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;55:905-914. doi:10.1093/cid/cis580
Galloway-Pena 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;122:2186-2196. doi:10.1002/cncr.30039
Taur Y, Jenq RR, Perales MA, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124:1174-1182. doi:10.1182/blood-2014-02-554725
Staffas A, Burgos da Silva M, van den Brink MRM. The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease. Blood. 2017;129:927-933. doi:10.1182/blood-2016-09-691394
Kakihana K, Fujioka Y, Suda W, et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. 2016;128:2083-2088. doi:10.1182/blood-2016-05-717652
DeFilipp Z, Peled JU, Li S, et al. Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv. 2018;2:745-753. doi:10.1182/bloodadvances.2018017731
Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555:623-628. doi:10.1038/nature25979
Vangay P, Johnson AJ, Ward TL, et al. US immigration westernizes the human gut microbiome. Cell. 2018;175:962-972.e10. doi:10.1016/j.cell.2018.10.029
Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci U S A. 2008;105:20858-20863. doi:10.1073/pnas.0808723105
Kim S, Covington A, Pamer EG. The intestinal microbiota: antibiotics, colonization resistance, and enteric pathogens. Immunol Rev. 2017;279:90-105. doi:10.1111/imr.12563
Galloway-Pena JR, Smith DP, Sahasrabhojane P, et al. Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients. Genome Med. 2017;9:21. doi:10.1186/s13073-017-0409-1
Rashidi A, Kaiser T, Shields-Cutler R, et al. Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia. Sci Rep. 2019;9:6083. doi:10.1038/s41598-019-42652-6
Rashidi A, Kaiser T, Holtan SG, Weisdorf DJ, Khoruts A, Staley C. Pre-transplant recovery of microbiome diversity without recovery of the original microbiome. Bone Marrow Transplant. 2019;54:1115-1117. doi:10.1038/s41409-018-0414-z
Caporaso JG, Lauber CL, Walters WA, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6:1621-1624. doi:10.1038/ismej.2012.8
Gohl DM, Vangay P, Garbe J, et al. Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies. Nat Biotechnol. 2016;34:942-949. doi:10.1038/nbt.3601
Schloss PD, Westcott SL, Ryabin T, et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009;75:7537-7541. doi:10.1128/AEM.01541-09
Aronesty E. Comparison of sequencing utility programs. Open Bioinformatics J. 2013;7:1-8. doi:10.2174/1875036201307010001
Pruesse E, Quast C, Knittel K, et al. SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res. 2007;35:7188-7196. doi:10.1093/nar/gkm864
Schloss PD, Westcott SL. Assessing and improving methods used in operational taxonomic unit-based approaches for 16S rRNA gene sequence analysis. Appl Environ Microbiol. 2011;77:3219-3226. doi:10.1128/AEM.02810-10
Huse SM, Welch DM, Morrison HG, Sogin ML. Ironing out the wrinkles in the rare biosphere through improved OTU clustering. Environ Microbiol. 2010;12:1889-1898. doi:10.1111/j.1462-2920.2010.02193.x
Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27:2194-2200. doi:10.1093/bioinformatics/btr381
Cole JR, Wang Q, Cardenas E, et al. The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic Acids Res. 2009;37:D141-D145. doi:10.1093/nar/gkn879
Schloss PD. The effects of alignment quality, distance calculation method, sequence filtering, and region on the analysis of 16S rRNA gene-based studies. PLoS Comput Biol. 2010;6:e1000844. doi:10.1371/journal.pcbi.1000844
Weiss S, Xu ZZ, Peddada S, et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome. 2017;5:27. doi:10.1186/s40168-017-0237-y
Shannon CE, Weaver W. The Mathematical Theory of Communication. University of Illinois Press; 1949.
Bray JR, Curtis JT. An ordination of the upland forest communities of southern Wisconsin. Ecol Monogr. 1957;27:325-349.
Clarke KR. Non-parametric multivariate analyses of changes in community structure. Aust J Ecol. 1993;18:117-143.
Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60. doi:10.1186/gb-2011-12-6-r60
Wilkinson G, Rogers C. Symbolic description of factorial models for analysis of variance. J R Stat Soc Ser C. 1973;22:392-399.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57:289-300.
Raymond F, Ouameur AA, Deraspe M, et al. The initial state of the human gut microbiome determines its reshaping by antibiotics. ISME J. 2016;10:707-720. doi:10.1038/ismej.2015.148
Sghir A, Gramet G, Suau A, Rochet V, Pochart P, Dore J. Quantification of bacterial groups within human fecal flora by oligonucleotide probe hybridization. Appl Environ Microbiol. 2000;66:2263-2266. doi:10.1128/aem.66.5.2263-2266.2000
Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635-1638. doi:10.1126/science.1110591
Almonacid DE, Kraal L, Ossandon FJ, et al. 16S rRNA gene sequencing and healthy reference ranges for 28 clinically relevant microbial taxa from the human gut microbiome. PLoS One. 2017;12:e0176555. doi:10.1371/journal.pone.0176555
Holtan SG, DeFor TE, Lazaryan A, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333-1338. doi:10.1182/blood-2014-10-609032
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;49:262-270. doi:10.1086/599346
Weber D, Oefner PJ, Hiergeist A, et al. Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood. 2015;126:1723-1728. doi:10.1182/blood-2015-04-638858
Weber D, Hiergeist A, Weber M, et al. Detrimental effect of broad-spectrum antibiotics on intestinal microbiome diversity in patients after allogeneic stem cell transplantation: lack of commensal sparing antibiotics. Clin Infect Dis. 2019;68:1303-1310. doi:10.1093/cid/ciy711
Pessione E. Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. Front Cell Infect Microbiol. 2012;2:86. doi:10.3389/fcimb.2012.00086
Kommineni S, Bretl DJ, Lam V, et al. Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract. Nature. 2015;526:719-722. doi:10.1038/nature15524
Webb BJ, Healy R, Majers J, et al. Prediction of bloodstream infection due to vancomycin-resistant Enterococcus in patients undergoing leukemia induction or hematopoietic stem-cell transplantation. Clin Infect Dis. 2017;64:1753-1759. doi:10.1093/cid/cix232
Ubeda C, Bucci V, Caballero S, et al. Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect Immun. 2013;81:965-973. doi:10.1128/IAI.01197-12
Caballero S, Kim S, Carter RA, et al. Cooperating commensals restore colonization resistance to vancomycin-resistant Enterococcus faecium. Cell Host Microbe. 2017;21:592-602.e4. doi:10.1016/j.chom.2017.04.002
Ford CD, Coombs J, Stofer MG, et al. Decrease in vancomycin-resistant Enterococcus colonization associated with a reduction in carbapenem use as empiric therapy for febrile neutropenia in patients with acute leukemia. Infect Control Hosp Epidemiol. 2019;40:774-779. doi:10.1017/ice.2019.93
Morjaria S, Schluter J, Taylor BP, et al. Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation. Infect Immun. 2019;87:e00206-19. doi:10.1128/IAI.00206-19
Shono Y, Docampo MD, Peled JU, et al. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. Sci Transl Med. 2016;8:339ra71. doi:10.1126/scitranslmed.aaf2311
Ubeda C, Taur Y, Jenq RR, et al. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest. 2010;120:4332-4341. doi:10.1172/JCI43918
Garcia-Vidal C, Cardozo-Espinola C, Puerta-Alcalde P, et al. Risk factors for mortality in patients with acute leukemia and bloodstream infections in the era of multiresistance. PLoS One. 2018;13:e0199531. doi:10.1371/journal.pone.0199531
Anderson RC, Cookson AL, McNabb WC, et al. Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation. BMC Microbiol. 2010;10:316. doi:10.1186/1471-2180-10-316
Karczewski J, Troost FJ, Konings I, et al. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Liver Physiol. 2010;298:G851-G859. doi:10.1152/ajpgi.00327.2009
Rashidi A, Wangjam T, Bhatt AS, Weisdorf DJ, Holtan SG; BMT CTN Investigators. Antibiotic practice patterns in hematopoietic cell transplantation: a survey of blood and marrow transplant clinical trials network centers. Am J Hematol. 2018;93:E348-E350. doi:10.1002/ajh.25236