3,028
Views
6
CrossRef citations to date
0
Altmetric
Original Article

Citizen-science based study of the oral microbiome in Cystic fibrosis and matched controls reveals major differences in diversity and abundance of bacterial and fungal species

, , , , , , , , , , , , , , & ORCID Icon show all
Article: 1897328 | Received 12 Nov 2020, Accepted 26 Feb 2021, Published online: 17 May 2021

References

  • Zielenski J, Rozmahel R, Bozon D, et al. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics. 1991;10:214–17.
  • Bassett DE Jr, Boguski MS, Hieter P. Yeast genes and human disease. Nature. 1996;379:589–590.
  • Saint-Criq V, Gray MA. Role of CFTR in epithelial physiology. Cell Mol Life Sci. 2017;74:93–115.
  • Tilley AE, Walters MS, Shaykhiev R, et al. Cilia dysfunction in lung disease. Annu Rev Physiol. 2015;77:379–406.
  • Taylor CJ, McGaw J, Howden R, et al. Bacterial reservoirs in cystic fibrosis. Arch Dis Child. 1990;65:175–177.
  • Marshall BC, Elbert A, Petren K, et al. Cystic fibrosis foundation patient registry 2014 annual data report. Bethesda, Maryland: Cystic Fibrosis Foundation; 2015.
  • Rosenfeld M, Emerson J, McNamara S, et al. Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort. J Cyst Fibros. 2012;11:446–453.
  • Saiman L, Siegel J. Cystic fibrosis foundation consensus conference on infection control participants. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission. Am J Infect Control. 2003;31:S1–62. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12762292
  • Rivas Caldas R, Le Gall F, Revert K, et al. Pseudomonas aeruginosa and periodontal pathogens in the oral cavity and lungs of cystic fibrosis patients: a case-control study. J Clin Microbiol. 2015;53:1898–1907.
  • Boutin S, Graeber SY, Weitnauer M, et al. Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis. PLoS One. 2015;10:e0116029.
  • Gomes-Filho IS, Passos JS, Seixas Da Cruz S. Respiratory disease and the role of oral bacteria. J Oral Microbiol. 2010;2:5811.
  • Whiteson KL, Bailey B, Bergkessel M, et al. The upper respiratory tract as a microbial source for pulmonary infections in cystic fibrosis. Parallels from island biogeography. Am J Respir Crit Care Med. 2014;189:1309–1315.
  • Dickson RP, Erb-Downward JR, Freeman CM, et al. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann Am Thorac Soc. 2015;12:821–830.
  • Pawlaczyk-Kamieńska T, Borysewicz-Lewicka M, Batura-Gabryel H. Salivary biomarkers and oral microbial load in relation to the dental status of adults with cystic fibrosis. Microorganisms. 2019;7:7.
  • Tate S, MacGregor G, Davis M, et al. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax. 2002;57:926–929.
  • Kunzelmann K, Schreiber R, Hadorn HB. Bicarbonate in cystic fibrosis. J Cyst Fibros. 2017;16:653–662.
  • Cuthbertson L, Walker AW, Oliver AE, et al. Lung function and microbiota diversity in cystic fibrosis. Microbiome. 2020;8:45.
  • Blainey PC, Milla CE, Cornfield DN, et al. Quantitative analysis of the human airway microbial ecology reveals a pervasive signature for cystic fibrosis. Sci Transl Med. 2012;4:153ra130.
  • Coburn B, Wang PW, Diaz Caballero J, et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep. 2015;5:10241.
  • Cox MJ, Allgaier M, Taylor B, et al. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One. 2010;5:e11044.
  • Zemanick ET, Wagner BD, Robertson CE, et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J. 2017;50:50.
  • Baliga S, Muglikar S, Kale R. Salivary pH: a diagnostic biomarker. J Indian Soc Periodontol. 2013;17:461–465.
  • Prasad M, Toshi SR, Mallik M, et al. Periodontal disease and salivary pH: case control study. Int Arch Integr Med. 2019;6:1–6. Available from: https://imsear.searo.who.int/jspui/handle/123456789/187183
  • Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res. 1994;8:263–271.
  • LaMonte MJ, Genco RJ, Zheng W, et al. Substantial differences in the subgingival microbiome measured by 16S metagenomics according to periodontitis status in older women. Dent J. 2018;6. DOI:https://doi.org/10.3390/dj6040058.
  • Abusleme L, Dupuy AK, Dutzan N, et al. The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. Isme J. 2013;7:1016–1025.
  • Genco RJ, LaMonte MJ, McSkimming DI, et al. The subgingival microbiome relationship to periodontal disease in older women. J Dent Res. 2019;98:975–984.
  • Takeshita T, Kageyama S, Furuta M, et al. Bacterial diversity in saliva and oral health-related conditions: the Hisayama study. Sci Rep. 2016;6:22164.
  • Catalán MA, Scott-Anne K, Klein MI, et al. Elevated incidence of dental caries in a mouse model of cystic fibrosis. PLoS One. 2011;6:e16549.
  • Pawlaczyk-Kamieńska T, Borysewicz-Lewicka M, Śniatała R, et al. Dental and periodontal manifestations in patients with cystic fibrosis - A systematic review. J Cyst Fibros. 2019;18:762–771.
  • Arquitt CK, Boyd C, Wright JT. Cystic fibrosis transmembrane regulator gene (CFTR) is associated with abnormal enamel formation. J Dent Res. 2002;81:492–496.
  • Bronckers A, Kalogeraki L, Jorna HJN, et al. The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in maturation stage ameloblasts, odontoblasts and bone cells. Bone. 2010;46:1188–1196.
  • Ajonuma L, Lu Q, Cheung BPK, et al. Expression and localization of cystic fibrosis transmembrane conductance regulator in human gingiva. Cell Biol Int. 2010;34:147–152.
  • Herman K, Kowalczyk-Zając M, Pytrus T. Oral cavity health among cystic fibrosis patients: literature overview. Adv Clin Exp Med. 2017;26:1147–1153.
  • Willis JR, González-Torres P, Pittis AA, et al. Citizen science charts two major “stomatotypes” in the oral microbiome of adolescents and reveals links with habits and drinking water composition. Microbiome. 2018;6:218.
  • National Academies of Sciences, Engineering, and Medicine, Division of Behavioral and Social Sciences and Education, Board on Science Education, Committee on Designing Citizen Science to Support Science Learning. Learning through citizen science: enhancing opportunities by design. Dibner KA, Pandya R, editors. Washington (DC): National Academies Press (US); 2019. doi:https://doi.org/10.17226/25183.
  • Gura T. Citizen science: amateur experts. Nature. 2013;496:259–261.
  • Willis JR, Saus E, Iraola-Guzmán S, et al. Oral microbiome in down syndrome and its implications on oral health. Manuscript submitted for publication. J Oral Microbiol. 2021;13(1):1865690.
  • Altschul SF, Gish W, Miller W, et al. Basic local alignment search tool. J Mol Biol. 1990;215:403–410.
  • Callahan BJ, McMurdie PJ, Rosen MJ, et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–583.
  • Callahan BJ. DADA2 Pipeline tutorial. 1(16). In: DADA2 [Internet]. [cited 2020 Jul 9]. Available from: https://benjjneb.github.io/dada2/tutorial.html
  • Callahan B. Silva taxonomic training data formatted for DADA2 (Silva version 132). Zenodo; 2018. DOI:https://doi.org/10.5281/ZENODO.1172783.
  • Callahan BJ, Sankaran K, Fukuyama JA, et al. Bioconductor workflow for microbiome data analysis: from raw reads to community analyses. F1000Res. 2016;5:1492.
  • Wright ES. Using DECIPHER v2. 0 to analyze big biological sequence data in R. R J. 2016;8:352. Available from: https://journal.r-project.org/archive/2016/RJ-2016-025/index.html
  • Schliep KP. phangorn: phylogenetic analysis in R. Bioinformatics. 2011;27:592–593.
  • Palarea-Albaladejo J, Martín-Fernández JA. zCompositions — r package for multivariate imputation of left-censored data under a compositional approach. Chemometrics Intellig Lab Syst. 2015;143:85–96.
  • Gloor GB, Wu JR, Pawlowsky-Glahn V, et al. It’s all relative: analyzing microbiome data as compositions. Ann Epidemiol. 2016;26:322–329.
  • Gloor GB, Reid G. Compositional analysis: a valid approach to analyze microbiome high-throughput sequencing data. Can J Microbiol. 2016;62:692–703.
  • McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013;8:e61217.
  • Oksanen J, Blanchet FG, Friendly M, et al. Vegan: community ecology package. 2019. Available from: https://CRAN.R-project.org/package=vegan
  • Templ M, Hron K, Filzmoser P. robCompositions: an R-package for robust statistical analysis of compositional data. In: Templ M, Hron K, Filzmoser P, editors. Compositional data analysis: theory and applications. London: John Wiley and Sons; 2011. p. 341–355.
  • R Core Team. R: a language and environment for statistical computing. R foundation for statistical computing; 2020. Available from: https://www.R-project.org/
  • Fox J, Weisberg S. An R companion to applied regression. Third ed. Thousand Oaks, CA: Sage; 2019. Available from: https://socialsciences.mcmaster.ca/jfox/Books/Companion/
  • Faust K, Bauchinger F, De Buyl S, et al. seqtime: time series analysis of sequencing data. Github; 2020. Available from: https://github.com/hallucigenia-sparsa/seqtime
  • Kurtz ZD, Müller CL, Miraldi ER, et al. Sparse and compositionally robust inference of microbial ecological networks. PLoS Comput Biol. 2015;11:e1004226.
  • Faust K Microbial association network construction tutorial. 2017. Available from: http://psbweb05.psb.ugent.be/conet/microbialnetworks/spieceasi.php
  • Filosi M, Visintainer R, Riccadonna S. nettools: a network comparison framework. Cran; 2017.
  • Lambiase A, Del Pezzo M, Raia V, et al. Chryseobacterium respiratory tract infections in patients with cystic fibrosis. J Infect. 2007;55:518–523.
  • Coenye T, Goris J, Spilker T, et al. Characterization of unusual bacteria isolated from respiratory secretions of cystic fibrosis patients and description of inquilinus limosus gen. nov., sp. nov. J Clin Microbiol. 2002;40:2062–2069.
  • Fernández-Olmos A, García-Castillo M, Morosini M-I, et al. MALDI-TOF MS improves routine identification of non-fermenting gram negative isolates from cystic fibrosis patients. J Cyst Fibros. 2012;11:59–62.
  • Sharma P, Diene SM, Gimenez G, et al. Genome sequence of microbacterium yannicii, a bacterium isolated from a cystic fibrosis patient. J Bacteriol. 2012;194:4785.
  • Sharma P, Diene SM, Thibeaut S, et al. Phenotypic and genotypic properties of Microbacterium yannicii, a recently described multidrug resistant bacterium isolated from a lung transplanted patient with cystic fibrosis in France. BMC Microbiol. 2013;13:97.
  • Menuet M, Bittar F, Stremler N, et al. First isolation of two colistin-resistant emerging pathogens, brevundimonas diminuta and ochrobactrum anthropi, in a woman with cystic fibrosis: a case report. J Med Case Rep. 2008;2:373.
  • Carter C. Bioinformatics analysis of homologies between pathogen antigens, autoantigens and the CFTR cystic fibrosis protein: a role for immunoadsorption therapy? Nat Precedings. 2010. DOI:https://doi.org/10.1038/npre.2010.5352.1
  • Razvi S, Quittell L, Sewall A, et al. Respiratory microbiology of patients with cystic fibrosis in the USA, 1995 to 2005. Chest. 2009;136:1554–1560.
  • Hauser AR, Jain M, Bar-Meir M, et al. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev. 2011;24:29–70.
  • Talmaciu I, Varlotta L, Mortensen J, et al. Risk factors for emergence of Stenotrophomonas maltophilia in cystic fibrosis. Pediatr Pulmonol. 2000;30:10–15.
  • Paganin P, Fiscarelli EV, Tuccio V, et al. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function. PLoS One. 2015;10:e0124348.
  • Maeda Y, Elborn JS, Parkins MD, et al. Population structure and characterization of viridans group streptococci (VGS) including streptococcus pneumoniae isolated from adult patients with cystic fibrosis (CF). J Cyst Fibros. 2011;10:133–139.
  • García-Castillo M, Morosini MI, Valverde A, et al. Differences in biofilm development and antibiotic susceptibility among streptococcus pneumoniae isolates from cystic fibrosis samples and blood cultures. J Antimicrob Chemother. 2007;59:301–304.
  • Whiteson KL, Meinardi S, Lim YW, et al. Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2,3-butanedione fermentation. Isme J. 2014;8:1247–1258.
  • Lim YW, Schmieder R, Haynes M, et al. Mechanistic model of Rothia mucilaginosa adaptation toward persistence in the CF lung, based on a genome reconstructed from metagenomic data. PLoS One. 2013;8:e64285.
  • Sánchez-Bautista A, Rodríguez-Díaz JC, Garcia-Heredia I, et al. Airway microbiota in patients with paediatric cystic fibrosis: relationship with clinical status. Enferm Infecc Microbiol Clin. 2019;37:167–171.
  • De Dios Caballero J, Del Campo R, Royuela A, et al. Bronchopulmonary infection-colonization patterns in Spanish cystic fibrosis patients: results from a national multicenter study. J Cyst Fibros. 2016;15:357–365.
  • Tabatabaei M, Dastbarsar M, Moslehi MA. Isolation and identification of Pandoraea spp. From bronchoalveolar lavage of cystic fibrosis patients in Iran. Ital J Pediatr. 2019;45:118.
  • Filkins LM, Hampton TH, Gifford AH, et al. Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability. J Bacteriol. 2012;194:4709–4717.
  • Soret P, Vandenborght L-E, Francis F, et al. Respiratory mycobiome and suggestion of inter-kingdom network during acute pulmonary exacerbation in cystic fibrosis. Sci Rep. 2020;10:3589.
  • Worlitzsch D, Rintelen C, Böhm K, et al. Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients. Clin Microbiol Infect. 2009;15:454–460.
  • Zhao J, Schloss PD, Kalikin LM, et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A. 2012;109:5809–5814.
  • Coffey MJ, Nielsen S, Wemheuer B, et al. Gut microbiota in children with cystic fibrosis: a taxonomic and functional dysbiosis. Sci Rep. 2019;9:18593.
  • Bakare N, Rickerts V, Bargon J, et al. Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis. Mycoses. 2003;46:19–23.
  • Valenza G, Tappe D, Turnwald D, et al. Prevalence and antimicrobial susceptibility of microorganisms isolated from sputa of patients with cystic fibrosis. J Cyst Fibros. 2008;7:123–127.
  • Chotirmall SH, O’Donoghue E, Bennett K, et al. Sputum Candida albicans presages FEV₁ decline and hospital-treated exacerbations in cystic fibrosis. Chest. 2010;138:1186–1195.
  • Lepesqueur LSS, Tanaka MH, Lima De MGG, et al. Oral prevalence and antifungal susceptibility of Candida species in cystic fibrosis patients. Arch Oral Biol. 2020;116:104772.
  • Scoffield JA, Wu H. Oral streptococci and nitrite-mediated interference of Pseudomonas aeruginosa. Infect Immun. 2015;83:101–107.
  • Whiley RA, Fleming EV, Makhija R, et al. Environment and colonisation sequence are key parameters driving cooperation and competition between Pseudomonas aeruginosa cystic fibrosis strains and oral commensal streptococci. PLoS One. 2015;10:e0115513.
  • Boutin S, Dalpke AH. Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients. Mol Cell Pediatr. 2017;4:1.
  • Yuan Z, Panchal D, Syed MA, et al. Induction of cyclooxygenase-2 signaling by Stomatococcus mucilaginosus highlights the pathogenic potential of an oral commensal. J Immunol. 2013;191:3810–3817.
  • Gao B, Gallagher T, Zhang Y, et al. Tracking polymicrobial metabolism in cystic fibrosis airways: Pseudomonas aeruginosa metabolism and physiology are influenced by Rothia mucilaginosa-derived metabolites. mSphere. 2018;3. DOI:https://doi.org/10.1128/mSphere.00151-18.
  • Bensel T, Stotz M, Borneff-Lipp M, et al. Lactate in cystic fibrosis sputum. J Cyst Fibros. 2011;10:37–44.
  • Widdel F, Pfennig N. Studies on dissimilatory sulfate-reducing bacteria that decompose fatty acids II. Incomplete oxidation of propionate by Desulfobulbus propionicus gen. nov., sp. nov. Arch Microbiol. 1982;131:360–365.
  • Robinson CV, Elkins MR, Bialkowski KM, et al. Desulfurization of mucin by Pseudomonas aeruginosa: influence of sulfate in the lungs of cystic fibrosis patients. J Med Microbiol. 2012;61:1644–1653.
  • Scott J, Sueiro-Olivares M, Ahmed W, et al. Pseudomonas aeruginosa-derived volatile sulfur compounds promote distal aspergillus fumigatus growth and a synergistic pathogen-pathogen interaction that increases pathogenicity in co-infection. Front Microbiol. 2019;10:2311.
  • Mohapatra NK, Cheng PW, Parker JC, et al. Alteration of sulfation of glycoconjugates, but not sulfate transport and intracellular inorganic sulfate content in cystic fibrosis airway epithelial cells. Pediatr Res. 1995;38:42–48.
  • Zhang Y, Doranz B, Yankaskas JR, et al. Genotypic analysis of respiratory mucous sulfation defects in cystic fibrosis. J Clin Invest. 1995;96:2997–3004.
  • Foweraker J. Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br Med Bull. 2009;89:93–110.
  • Mohanty R, Asopa SJ, Joseph MD, et al. Red complex: polymicrobial conglomerate in oral flora: a review. J Family Med Prim Care. 2019;8:3480–3486.
  • Colombo APV, Boches SK, Cotton SL, et al. Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. J Periodontol. 2009;80:1421–1432.
  • Koyanagi T, Sakamoto M, Takeuchi Y, et al. Comprehensive microbiological findings in peri-implantitis and periodontitis. J Clin Periodontol. 2013;40:218–226.
  • Riggio MP, Lennon A. Development of a PCR assay specific for peptostreptococcus anaerobius. J Med Microbiol. 2002;51:1097–1101.
  • Bizzarro S, Laine ML, Buijs MJ, et al. Microbial profiles at baseline and not the use of antibiotics determine the clinical outcome of the treatment of chronic periodontitis. Sci Rep. 2016;6:20205.
  • Ramanan P, Barreto JN, Osmon DR, et al. Rothia bacteremia: a 10-year experience at Mayo Clinic, Rochester, Minnesota. J Clin Microbiol. 2014;52:3184–3189.
  • Ruhl S, Eidt A, Melzl H, et al. Probing of microbial biofilm communities for coadhesion partners. Appl Environ Microbiol. 2014;80:6583–6590.
  • Zhou J, Jiang N, Wang S, et al. Exploration of human salivary microbiomes–insights into the novel characteristics of microbial community structure in caries and caries-free subjects. PLoS One. 2016;11:e0147039.
  • Chen H, Ling Z, Wen J, et al. Oral microbiota in chinese she children with dental caries. IADR/AADR/CADR General Session and Exhibition. J Dent Res;2013. [cited 2020 Aug 14].
  • Jiang Q, Liu J, Chen L, et al. The oral microbiome in the elderly with dental caries and health. Front Cell Infect Microbiol. 2018;8:442.
  • Mantzourani M, Gilbert SC, Sulong HNH, et al. The isolation of bifidobacteria from occlusal carious lesions in children and adults. Caries Res. 2009;43:308–313.
  • Tanner ACR, Kent RL Jr, Holgerson PL, et al. Microbiota of severe early childhood caries before and after therapy. J Dent Res. 2011;90:1298–1305.
  • Jiang W, Ling Z, Lin X, et al. Pyrosequencing analysis of oral microbiota shifting in various caries states in childhood. Microb Ecol. 2014;67:962–969.
  • Henne K, Rheinberg A, Melzer-Krick B, et al. Aciduric microbial taxa including scardovia wiggsiae and bifidobacterium spp. in caries and caries free subjects. Anaerobe. 2015;35:60–65.
  • Richards VP, Alvarez AJ, Luce AR, et al. Microbiomes of site-specific dental plaques from children with different caries status. Infect Immun. 2017;85:85.
  • Wang Y, Zhang J, Chen X, et al. Profiling of oral microbiota in early childhood caries using single-molecule real-time sequencing. Front Microbiol. 2017;8:2244.
  • Naidu BV, Reginald BA. Quantification and correlation of oral Candida with caries index among different age groups of school children: a case-control study. Ann Med Health Sci Res. 2016;6:80–84.
  • Lozano Moraga CP, Rodríguez Martínez GA, Lefimil Puente CA, et al. Prevalence of Candida albicans and carriage of Candida non-albicans in the saliva of preschool children, according to their caries status. Acta Odontol Scand. 2017;75:30–35.
  • Xiao J, Huang X, Alkhers N, et al. Candida albicans and early childhood caries: a systematic review and meta-analysis. Caries Res. 2018;52:102–112.
  • Eidt G, De Andrade CG, De Negrini TC, et al. Role of Candida albicans on enamel demineralization and on acidogenic potential of streptococcus mutans in vitro biofilms. J Appl Oral Sci. 2019;27:e20180593.
  • Xu L, Chen X, Wang Y, et al. Dynamic alterations in salivary microbiota related to dental caries and age in preschool children with deciduous dentition: a 2-year follow-up study. Front Physiol. 2018;9:342.
  • Xu H, Hao W, Zhou Q, et al. Plaque bacterial microbiome diversity in children younger than 30 months with or without caries prior to eruption of second primary molars. PLoS One. 2014;9:e89269.
  • Lif Holgerson P, Öhman C, Rönnlund A, et al. Maturation of oral microbiota in children with or without dental caries. PLoS One. 2015;10:e0128534.
  • Schoilew K, Ueffing H, Dalpke A, et al. Bacterial biofilm composition in healthy subjects with and without caries experience. J Oral Microbiol. 2019;11:1633194.
  • Hernández M, Planells P, Martínez E, et al. Microbiology of molar-incisor hypomineralization lesions. A pilot study. J Oral Microbiol. 2020;12:1766166.
  • Henskens YM, Van Den Keijbus PA, Veerman EC, et al. Protein composition of whole and parotid saliva in healthy and periodontitis subjects. Determination of cystatins, albumin, amylase and IgA. J Periodontal Res. 1996;31:57–65.
  • Qu XM, Wu ZF, Pang BX, et al. From nitrate to nitric oxide: the role of salivary glands and oral bacteria. J Dent Res. 2016;95:1452–1456.
  • Espinoza JL, Harkins DM, Torralba M, et al. Supragingival plaque microbiome ecology and functional potential in the context of health and disease. MBio. 2018;9:9.
  • Grasemann H, Ioannidis I, Tomkiewicz RP, et al. Nitric oxide metabolites in cystic fibrosis lung disease. Arch Dis Child. 1998;78:49–53.
  • Zetterquist W, Marteus H, Kalm-Stephens P, et al. Oral bacteria–the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis. Respir Med. 2009;103:187–193.
  • De Winter-de Groot KM, Van Der Ent CK. Nitric oxide in cystic fibrosis. J Cyst Fibros. 2005;4(Suppl 2):25–29.
  • Kerley CP, Kilbride E, Greally P, et al. Dietary nitrate acutely and markedly increased exhaled nitric oxide in a cystic fibrosis case. Clin Med Res. 2016;14:151–155.
  • Nawaz A, Hasan F, Shah AA. Degradation of poly(ɛ-caprolactone) (PCL) by a newly isolated Brevundimonas sp. strain MRL-AN1 from soil. FEMS Microbiol Lett. 2015;362:1–7.
  • Al-Jebouri M. The relationship between periodontal disease and predisposing factors. Tikrit J Dental Sci. 2016;4:68–80.
  • Colombo APV, Bennet S, Cotton SL, et al. Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: comparison between good responders and individuals with refractory periodontitis using the human oral microbe identification microarray. J Periodontol. 2012;83:1279–1287.
  • Kõll‐Klais P, Mändar R, Leibur E. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol. 2005;20:354–361.
  • Chatterjee A, Bhattacharya H Probiotics in periodontal health and disease. society of periodontology. 2011. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3134041/
  • Eribe ERK, Olsen I. Leptotrichia species in human infections. Anaerobe. 2008;14:131–137.
  • Peterson SN, Snesrud E, Liu J, et al. The dental plaque microbiome in health and disease. PLoS One. 2013;8:e58487.
  • Thompson J, Pikis A. Metabolism of sugars by genetically diverse species of oral Leptotrichia. Mol Oral Microbiol. 2012;27:34–44.
  • Losada PM, Chouvarine P, Dorda M, et al. The cystic fibrosis lower airways microbial metagenome. ERJ Open Res. 2016;2. DOI:https://doi.org/10.1183/23120541.00096-2015.
  • Nielsen S, Needham B, Leach ST, et al. Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis. Sci Rep. 2016;6:24857.
  • Zakharkina T, Heinzel E, Koczulla RA, et al. Analysis of the airway microbiota of healthy individuals and patients with chronic obstructive pulmonary disease by T-RFLP and clone sequencing. PLoS One. 2013;8:e68302.
  • Nallabelli N, Patil PP, Pal VK, et al. Biochemical and genome sequence analyses of Megasphaera sp. strain DISK18 from dental plaque of a healthy individual reveals commensal lifestyle. Sci Rep. 2016;6:33665.
  • Dewhirst FE, Chen C-KC, Paster BJ, et al. Phylogeny of species in the family neisseriaceae isolated from human dental plaque and description of kingella orale sp. nov. Int J Syst Bacteriol. 1993;43:490–499.
  • Bittar F, Cassagne C, Bosdure E. Outbreak of corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, France. Emerg Infect Dis. 2010;16:1231–1236. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3298292/
  • Pivot D, Fanton A, Badell-Ocando E, et al. Carriage of a single strain of nontoxigenic corynebacterium diphtheriae bv. Belfanti (corynebacterium belfantii) in four patients with cystic fibrosis. J Clin Microbiol. 2019;57. DOI:https://doi.org/10.1128/JCM.00042-19.
  • Layeghifard M, Li H, Wang PW, et al. Microbiome networks and change-point analysis reveal key community changes associated with cystic fibrosis pulmonary exacerbations. NPJ Biofilms Microbiomes. 2019;5:1–12.
  • Carrouel F, Viennot S, Santamaria J, et al. Quantitative molecular detection of 19 major pathogens in the interdental biofilm of periodontally healthy young adults. Front Microbiol. 2016;7:840.
  • Mashima I, Fujita M, Nakatsuka Y, et al. The distribution and frequency of oral veillonella spp. associated with chronic periodontitis. Int J Curr Microbiol App Sci. 2015 . [cited 2020 Oct 15]. Available from: https://www.semanticscholar.org/paper/e8d55ce20a438733917336d7671f9228506628ae
  • Haraszthy VI, Zambon JJ, Sreenivasan PK, et al. Identification of oral bacterial species associated with halitosis. J Am Dent Assoc. 2007;138:1113–1120.
  • Stephen AS, Naughton DP, Pizzey RL, et al. In vitro growth characteristics and volatile sulfur compound production of Solobacterium moorei. Anaerobe. 2014;26:53–57.
  • Stipanuk MH, Dominy JE Jr, Lee J-I, et al. Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J Nutr. 2006;136:1652S–1659S.
  • McKone EF, Shao J, Frangolias DD, et al. Variants in the glutamate-cysteine-ligase gene are associated with cystic fibrosis lung disease. Am J Respir Crit Care Med. 2006;174:415–419.
  • Conrad C, Lymp J, Thompson V, et al. Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial. J Cyst Fibros. 2015;14:219–227.
  • Carmody LA, Zhao J, Schloss PD, et al. Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann ATS. 2013;10:179–187.
  • Dani S, Prabhu A, Chaitra KR, et al. Assessment of streptococcus mutans in healthy versus gingivitis and chronic periodontitis: a clinico-microbiological study. Contemp Clin Dent. 2016;7:529–534.
  • Contardo MS, Díaz N, Lobos O, et al. Oral colonization by streptococcus mutans and its association with the severity of periodontal disease in adults. Revista Clínica de Periodoncia, Implantología y Rehabilitación Oral. 2011;4:9–12.
  • Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000. 2002;28:12–55.
  • Vandeplassche E, Tavernier S, Coenye T, et al. Influence of the lung microbiome on antibiotic susceptibility of cystic fibrosis pathogens. Eur Respir Rev. 2019;28:28.
  • Bevivino A, Bacci G, Drevinek P, et al. Deciphering the ecology of cystic fibrosis bacterial communities: towards systems-level integration. Trends Mol Med. 2019;25:1110–1122.
  • Jagathrakshakan SN, Sethumadhava RJ, Mehta DT, et al. 16S rRNA gene-based metagenomic analysis identifies a novel bacterial co-prevalence pattern in dental caries. Eur J Dent. 2015;9:127.
  • Basavaraju M, Sisnity VS, Palaparthy R, et al. Quorum quenching: signal jamming in dental plaque biofilms. J Dent Sci. 2016;11:349–352.
  • Utari PD, Vogel J, Quax WJ. Deciphering physiological functions of AHL quorum quenching acylases. Front Microbiol. 2017;8:1123.
  • Muras A, Otero-Casal P, Blanc V, et al. Acyl homoserine lactone-mediated quorum sensing in the oral cavity: a paradigm revisited. Sci Rep. 2020;10:9800.
  • Muras A, Mayer C, Otero-Casal P, et al. Short-Chain N-acylhomoserine lactone quorum-sensing molecules promote periodontal pathogens in in vitro oral biofilms. Appl Environ Microbiol. 2020;86:86.
  • Camelo-Castillo AJ, Mira A, Pico A, et al. Subgingival microbiota in health compared to periodontitis and the influence of smoking. Front Microbiol. 2015;6:119.
  • Ai D, Huang R, Wen J, et al. Integrated metagenomic data analysis demonstrates that a loss of diversity in oral microbiota is associated with periodontitis. BMC Genomics. 2017;18:1041.
  • Shin M, Han D, Yi H, et al. Characterization of subgingival microorganisms according to periodontitis and cardiovascular status. IADR/AADR/CADR General Session. J Dent Res; 2013.
  • Anesti V, McDonald IR, Ramaswamy M, et al. Isolation and molecular detection of methylotrophic bacteria occurring in the human mouth. Environ Microbiol. 2005;7:1227–1238.
  • Vielkind P, Jentsch H, Eschrich K, et al. Prevalence of actinomyces spp. in patients with chronic periodontitis. Int J Med Microbiol. 2015;305:682–688.
  • Chen W-P, Chang S-H, Tang C-Y, et al. Composition analysis and feature selection of the oral microbiota associated with periodontal disease. Biomed Res Int. 2018;2018:3130607.
  • Tindall BJ, Euzéby JP. Proposal of parvimonas gen. nov. and quatrionicoccus gen. nov. as replacements for the illegitimate, prokaryotic, generic names micromonas Murdoch and Shah 2000 and Quadricoccus Maszenan et al. 2002, respectively. Int J Syst Evol Microbiol. 2006;56:2711–2713.
  • Deng Z-L, Szafrański SP, Jarek M, et al. Dysbiosis in chronic periodontitis: key microbial players and interactions with the human host. Sci Rep. 2017;7:3703.
  • Naginyte M, Do T, Meade J, et al. Enrichment of periodontal pathogens from the biofilms of healthy adults. Sci Rep. 2019;9:5491.
  • Ghayoumi N, Chen C, Slots J. Dialister pneumosintes, a new putative periodontal pathogen. J Periodontal Res. 2002;37:75–78.
  • Oswal P, Katti S, Joshi V, et al. Identification of dialister pneumosintes in healthy and chronic periodontitis patients with type 2 diabetes mellitus and its correlation with the red complex bacteria. J Interdiscip Dent. 2020;10:17.