Oral microbiota distinguishes acute lymphoblastic leukemia pediatric hosts from healthy populations

Yan Wang, Jing Xue, Xuedong Zhou, Meng You, Qin Du, Xue Yang, Jinzhi He, Jing Zou, Lei Cheng, Mingyun Li, Yuqing Li, Yiping Zhu, Jiyao Li, Wenyuan Shi, Xin Xu, Yan Wang, Jing Xue, Xuedong Zhou, Meng You, Qin Du, Xue Yang, Jinzhi He, Jing Zou, Lei Cheng, Mingyun Li, Yuqing Li, Yiping Zhu, Jiyao Li, Wenyuan Shi, Xin Xu

Abstract

In leukemia, oral manifestations indicate aberrations in oral microbiota. Microbiota structure is determined by both host and environmental factors. In human hosts, how health status shapes the composition of oral microbiota is largely unknown. Taking advantage of advances in high-throughput sequencing, we compared the composition of supragingival plaque microbiota of acute lymphoblastic leukemia (ALL) pediatric patients with healthy controls. The oral microbiota of leukemia patients had lower richness and less diversity compared to healthy controls. Microbial samples clustered into two major groups, one of ALL patients and another of healthy children, with different structure and composition. Abundance changes of certain taxa including the Phylum Firmicutes, the Class Bacilli, the Order Lactobacillales, the Family Aerococcaceae and Carnobacteriaceae, as well as the Genus Abiotrophia and Granulicatella were associated with leukemia status. ALL patients demonstrated a structural imbalance of the oral microbiota, characterized by reduced diversity and abundance alterations, possibly involved in systemic infections, indicating the importance of immune status in shaping the structure of oral microbiota.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Dendrogram of OTU composition obtained…
Figure 1. Dendrogram of OTU composition obtained from acute lymphoblastic leukemia-affected children and healthy controls.
The dendrogram (left section) indicates the similarity of the microbial communities of supragingival dental plaque between subjects according to their OTU composition, as determined using the Jaccard index (MOTHUR). A summary of patients' clinical information is presented in the right section. H, healthy children. L, acute lymphoblastic leukemia-affected children. dmfs/DMFS, decayed-missing-filled surfaces index in primary and permanent teeth, respectively. G, gingivitis. ND, no data obtained.
Figure 2. Weighted Unifrac PCoA analysis.
Figure 2. Weighted Unifrac PCoA analysis.
The first two principal coordinates (PCo1 and PCo2) from the principal coordinate analysis of weighted UniFrac are plotted for each sample. The variance explained by the PCos is indicated in parentheses on the axes. H, healthy children. L, acute lymphoblastic leukemia-affected children.
Figure 3. Differential relative abundance of bacterial…
Figure 3. Differential relative abundance of bacterial taxonomy profiles of acute lymphoblastic leukemia and healthy subjects based on Metastats analysis.
Comparisons were performed at each of the taxonomical levels of Phylum (A), Class (B), Order (C), Family (D) and Genus (E). Means of the relative abundance for each taxon at each taxonomical level between the healthy and acute lymphoblastic leukemia host-populations are compared, with a p value threshold set at 0.05 (*p<0.05; **p<0.01) and a q value threshold at 0.5. The discriminating taxa (p<0.05 and q<0.5) with relative abundance >1% for at least one group at each level are shown. H, healthy children. L, acute lymphoblastic leukemia-affected children.

References

    1. Pui CH, Robison LL, Look AT (2008) Acute lymphoblastic leukaemia. Lancet 371: 1030–1043.
    1. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, et al. (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131: 33–45.
    1. Barrett AP (1986) Leukemic cell infiltration of the gingivae. J Periodontol 57: 579–581.
    1. Hou GL, Huang JS, Tsai CC (1997) Analysis of oral manifestations of leukemia: a retrospective study. Oral Dis 3: 31–38.
    1. Meyer U, Kleinheinz J, Handschel J, Kruse-Losler B, Weingart D, et al. (2000) Oral findings in three different groups of immunocompromised patients. J Oral Pathol Med 29: 153–158.
    1. Javed F, Utreja A, Bello Correa FO, Al-Askar M, Hudieb M, et al. (2012) Oral health status in children with acute lymphoblastic leukemia. Crit Rev Oncol Hematol 83: 303–309.
    1. Paunica SC, Dumitriu A, Mogos M, Georgescu O, Mogos I (2009) The evaluation of the periodontium in patients with leukemia using thermographic imaging. Hematology 14: 341–346.
    1. Khan SA, Wingard JR (2001) Infection and mucosal injury in cancer treatment. JNCI Monographs 2001: 31–36.
    1. Greenberg MS, Cohen SG, McKitrick JC, Cassileth PA (1982) The oral flora as a source of septicemia in patients with acute leukemia. Oral Surg Oral Med Oral Pathol 53: 32–36.
    1. Sixou JL, De Medeiros-Batista O, Gandemer V, Bonnaure-Mallet M (1998) The effect of chemotherapy on the supragingival plaque of pediatric cancer patients. Oral Oncol 34: 476–483.
    1. Wahlin YB, Granstrom S, Persson S, Sjostrom M (1991) Multivariate study of enterobacteria and Pseudomonas in saliva of patients with acute leukemia. Oral Surg Oral Med Oral Pathol 72: 300–308.
    1. O'Sullivan EA, Duggal MS, Bailey CC, Curzon ME, Hart P (1993) Changes in the oral microflora during cytotoxic chemotherapy in children being treated for acute leukemia. Oral Surg Oral Med Oral Pathol 76: 161–168.
    1. Galili D, Donitza A, Garfunkel A, Sela MN (1992) Gram-negative enteric bacteria in the oral cavity of leukemia patients. Oral Surg Oral Med Oral Pathol 74: 459–462.
    1. Kitchingman GR, Rovigatti U, Mauer AM, Melvin S, Murphy SB, et al. (1985) Rearrangement of immunoglobulin heavy chain genes in T cell acute lymphoblastic leukemia. Blood 65: 725–729.
    1. Zhang XL, Komada Y, Chipeta J, Li QS, Inaba H, et al. (2000) Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia. Cancer Immunol Immunother 49: 165–172.
    1. Li K, Bihan M, Methe BA (2013) Analyses of the stability and core taxonomic memberships of the human microbiome. PLoS One 8: e63139.
    1. Zaura E, Keijser BJ, Huse SM, Crielaard W (2009) Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol 9: 259.
    1. Lazarevic V, Whiteson K, Hernandez D, Francois P, Schrenzel J (2010) Study of inter- and intra-individual variations in the salivary microbiota. BMC Genomics 11: 523.
    1. Ling Z, Kong J, Jia P, Wei C, Wang Y, et al. (2010) Analysis of oral microbiota in children with dental caries by PCR-DGGE and barcoded pyrosequencing. Microb Ecol 60: 677–690.
    1. Yang F, Zeng X, Ning K, Liu KL, Lo CC, et al. (2012) Saliva microbiomes distinguish caries-active from healthy human populations. ISME J 6: 1–10.
    1. Saber MH, Schwarzberg K, Alonaizan FA, Kelley ST, Sedghizadeh PP, et al. (2012) Bacterial flora of dental periradicular lesions analyzed by the 454-pyrosequencing technology. J Endod 38: 1484–1488.
    1. Koren O, Spor A, Felin J, Fak F, Stombaugh J, et al. (2011) Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A 108 Suppl 1: 4592–4598.
    1. Hu YJ, Shao ZY, Wang Q, Jiang YT, Ma R, et al. (2013) Exploring the dynamic core microbiome of plaque microbiota during head-and-neck radiotherapy using pyrosequencing. PLoS One 8: e56343.
    1. Hu YJ, Wang Q, Jiang YT, Ma R, Xia WW, et al. (2013) Characterization of oral bacterial diversity of irradiated patients by high-throughput sequencing. Int J Oral Sci 5: 21–25.
    1. Hague A, Baechle M (2008) Advanced caries in a patient with a history of bariatric surgery. J Dent Hyg 82: 22.
    1. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, et al. (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437: 376–380.
    1. Wang Q, Garrity GM, Tiedje JM, Cole JR (2007) Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 73: 5261–5267.
    1. Lozupone C, Knight R (2005) UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 71: 8228–8235.
    1. Lozupone C, Hamady M, Knight R (2006) UniFrac–an online tool for comparing microbial community diversity in a phylogenetic context. BMC bioinformatics 7: 371.
    1. Schloss PD, Handelsman J (2006) Introducing TreeClimber, a test to compare microbial community structures. Appl Environ Microbiol 72: 2379–2384.
    1. White JR, Nagarajan N, Pop M (2009) Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol 5: e1000352.
    1. Krych L, Hansen CH, Hansen AK, van den Berg FW, Nielsen DS (2013) Quantitatively different, yet qualitatively alike: a meta-analysis of the mouse core gut microbiome with a view towards the human gut microbiome. PLoS One 8: e62578.
    1. Lucas VS, Beighton D, Roberts GJ, Challacombe SJ (1997) Changes in the oral streptococcal flora of children undergoing allogeneic bone marrow transplantation. J Infect 35: 135–141.
    1. Belstrøm D, Fiehn NE, Nielsen CH, Kirkby N, Twetman S, et al. (2014) Differences in bacterial saliva profile between periodontitis patients and a control cohort. J Clin Periodontol 41: 104–112.
    1. Colombo APV, Boches SK, Cotton SL, Goodson JM, Kent R, et al. (2009) Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. J Periodontol 80: 1421–1432.
    1. Mardis ER (2008) Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet 9: 387–402.
    1. van Vliet MJ, Tissing WJ, Dun CA, Meessen NE, Kamps WA, et al. (2009) 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 49: 262–270.
    1. Dethlefsen L, McFall-Ngai M, Relman DA (2007) An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature 449: 811–818.
    1. Hooper LV, Littman DR, Macpherson AJ (2012) Interactions between the microbiota and the immune system. Science 336: 1268–1273.
    1. von Rosenvinge EC, Song Y, White JR, Maddox C, Blanchard T, et al. (2013) Immune status, antibiotic medication and pH are associated with changes in the stomach fluid microbiota. ISME J 7: 1354–1366.
    1. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL (2003) Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422: 522–526.
    1. Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, et al. (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11: 76–83.
    1. Tlaskalová-Hogenová H, Štěpánková R, Hudcovic T, Tučková L, Cukrowska B, et al. (2004) Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 93: 97–108.
    1. Tjwa E, Mattijssen V (2008) Images in clinical medicine. Gingival hypertrophy and leukemia. N Engl J Med 359: e21.
    1. Hegde AM, Joshi S, Rai K, Shetty S (2011) Evaluation of oral hygiene status, salivary characteristics and dental caries experience in acute lymphoblastic leukemic (ALL) children. J Clin Pediatr Dent 35: 319–323.
    1. Phulpin-Weibel A, Gaspar N, Emirian A, Chachaty E, Valteau-Couanet D, et al. (2013) Intravascular catheter-related bloodstream infection caused by Abiotrophia defectiva in a neutropenic child. J Med Microbiol 62: 789–791.
    1. Senn L, Entenza JM, Greub G, Jaton K, Wenger A, et al. (2006) Bloodstream and endovascular infections due to Abiotrophia defectiva and Granulicatella species. BMC Infect Dis 6: 9.
    1. Cargill JS, Scott KS, Gascoyne-Binzi D, Sandoe JA (2012) Granulicatella infection: diagnosis and management. J Med Microbiol 61: 755–761.
    1. Liao CH, Teng LJ, Hsueh PR, Chen YC, Huang LM, et al. (2004) Nutritionally variant streptococcal infections at a University Hospital in Taiwan: disease emergence and high prevalence of beta-lactam and macrolide resistance. Clin Infect Dis 38: 452–455.
    1. Khan SA, Wingard JR (2001) Infection and mucosal injury in cancer treatment. J Natl Cancer Inst Monogr 31–36.

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