J. Bonder EZ. Contributed reagents/materials/analysis tools: MV BJFK WC. Wrote the paper: EAK M. J. Buijis M. J. Bonder MV BJFK WC EZ. References 1. Muenz R (2007) Aging and demographic change in European societies: main trends and alternative policy options. Social Protection: the World Bank. World B a n k w e b s i t e . A v a i l a b l e : h t t p : / / s i t e r e s o u r c e s . w o r l d b a n k . o r g / SOCIALPROTECTION/Resources/SP-Discussion-papers/Labor-Market- DP/0703.pdf. Accessed 2012 Feb 22. 2. Bodineau A, Folliguet M, Seguier S (2009) Tissular senescence and modifications of oral ecosystem in the elderly: risk factors for mucosal pathologies. Curr Aging Sci 2: 109–120. 3. Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, et al. (2010) Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathogens 6: e1000713. 4. ten Cate JM, Klis FM, Pereira-Cenci T, Crielaard W, de Groot PWJ (2009) Molecular and cellular mechanisms that lead to Candida biofilm formation. J Dent Res 88: 105–115. 5. Rocha Gusma˜o JM, Ferreira dos Santos SS, Piero Neisser M, Cardoso Jorge AO, Ivan Faria M (2010) Correlation between factors associated with the removable partial dentures use and Candida spp. in saliva. Gerodont 28: 283– 288. 6. Vanden Abbeele A, de Meel H, Ahariz M, Perraudin J-P, Beyer I, et al. (2008) Denture contamination by yeasts in the elderly. Gerodont 25: 222–228. 7. Pfaller MA, Diekema DJ (2010) Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 36: 1–53. 8. Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. New Engl J Med 348: 1546–1554. 9. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, et al. (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Inf Dis 39: 309–317. 10. Morales DK, Hogan DA (2010) Candida albicans interactions with bacteria in the context of human health and disease. PLoS Pathog 6: e1000886. 11. Jenkinson H, Douglas L (2002) Interactions between Candida species and bacteria in mixed infections. In: Brogden KA GJ, editor. Polymicrobial diseases. Washington, DC: ASM Press. 12. Shirtliff ME, Peters BM, Jabra-Rizk MA (2009) Cross-kingdom interactions: Candida albicans and bacteria. FEMS Microbiol Lett 299: 1–8. 13. Percival RS, Challacombe SJ, Marsh PD (1991) Age-related microbiological changes in the salivary and plaque microflora of healthy adults. J Med Microbiol 35: 5–11. 14. Ryu M, Ueda T, Saito T, Yasui M, Ishihara K, et al. (2010) Oral environmental factors affecting number of microbes in saliva of complete denture wearers. J Oral Rehabil 37: 194–201. 15. Zaura E, Keijser BJF, Huse SM, Crielaard W (2009) Defining the healthy ‘‘core microbiome’’ of oral microbial communities. BMC Microbiol 9: 259. 16. Crielaard W, Zaura E, Schuller AA, Huse SM, Montijn RC, et al. (2011) Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health. BMC Med Genomics 4: 22. 17. Gendreau L, Loewy ZG (2011) Epidemiology and etiology of denture stomatitis. J Prosthodont 20: 251–260. 18. Nasidze I, Li J, Quinque D, Tang K, Stoneking M (2009) Global diversity in the human salivary microbiome. Genome Res 19: 636–643. 19. Peters BM, Jabra-Rizk MA, O’May GA, Costerton JW, Shirtliff ME (2012) Polymicrobial interactions: Impact on pathogenesis and human disease. Clin Microbiol Rev 25: 193–213. 20. Li Y, Ku CYS, Xu J, Saxena D, Caufield PW (2005) Survey of Oral Microbial Diversity using PCR-based Denaturing Gradient Gel Electrophoresis. J Dent Res 84: 559–564. 21. Pham LC, van Spanning RJM, Ro¨ling WFM, Prosperi AC, Terefework Z, et al. (2009) Effects of probiotic Lactobacillus salivarius W24 on the compositional stability of oral microbial communities. Arch Oral Biol 54: 132–137. 22. Gihring TM, Green SJ, Schadt CW (2012) Massively parallel rRNA gene sequencing exacerbates the potential for biased community diversity compar- isons due to variable library sizes. Env Microbiol 14: 285–290. 23. Klinke T, Kneist S, de Soet JJ, Kuhlisch E, Mauersberger S, et al. (2009) Acid Production by Oral Strains of Candida albicans and Lactobacilli. Caries Res 43: 83–91. 24. Samaranayake LP, Hughes A, Weetman DA, MacFarlane TW (1986) Growth and acid production of Candida species in human saliva supplemented with glucose. J Oral Pathol 15: 251–254. 25. Holmes AR, van der Wielen P, Cannon RD, Ruske D, Dawes P (2006) Candida albicans binds to saliva proteins selectively adsorbed to silicone. Oral Surg Oral Medic Oral Pathol Oral Radiol Endodontol 102: 488–494. 26. Jenkinson HF, Lala HC, Shepherd MG (1990) Coaggregation of Streptococcus sanguis and other streptococci with Candida albicans. Infect Immun 58: 1429– 1436. 27. Richards S, Russell C (1987) The effect of sucrose on the colonization of acrylic by Candida albicans in pure and mixed culture in an artificial mouth. J Appl Microbiol 62: 421–427. Oral Candida and Salivary Microbiome 28. O’Sullivan JM, Jenkinson HF, Cannon RD (2000) Adhesion of Candida albicans to oral streptococci is promoted by selective adsorption of salivary proteins to the streptococcal cell surface. Microbiol 146: 41–48. 29. Holmes A, McNab R, Jenkinson H (1996) Candida albicans binding to the oral bacterium Streptococcus gordonii involves multiple adhesin-receptor interactions. Infect Immun 64: 4680–4685. 30. Boris S, Barbes C (2000) Role played by lactobacilli in controlling the population of vaginal pathogens. Microbes Infect 2: 543–546. 31. Nair RG, Anil S, Samaranayake LP (2001) The effect of oral bacteria on Candida albicans germ-tube formation. APMIS 109: 147–154. 32. Takahashi N, Nyvad B (2011) The role of bacteria in the caries process. Journal of Dental Research 90: 294–303. 33. Thein ZM, Samaranayake YH, Samaranayake LP (2006) Effect of oral bacteria on growth and survival of Candida albicans biofilms. Arch Oral Biol 51: 672–680. 34. Pybus V, Onderdonk AB (1998) A commensal symbiosis between Prevotella bivia and Peptostreptococcus anaerobius involves amino acids: potential significance to the pathogenesis of bacterial vaginosis. FEMS Immunol Med Microbiol 22: 317– 327. 35. Gordan VV, Garvan CW, Ottenga ME, Schulte R, Harris PA, et al. (2010) Could alkali production be considered an approach for caries control? Caries Res 44: 547–554. 36. Burne RA, Marquis RE (2000) Alkali production by oral bacteria and protection against dental caries. FEMS Microbiol Lett 193: 1–6. 37. Acevedo AM, Machado C, Rivera LE, Wolff M, Kleinberg I (2005) The inhibitory effect of an arginine bicarbonate/calcium carbonate CaviStat- containing dentifrice on the development of dental caries in Venezuelan school children. J Clin Dent 16: 63–70. 38. Huisman M, Poppelaars J, van der Horst M, Beekman AT, Brug J, et al. (2011) Cohort Profile: The Longitudinal Aging Study Amsterdam. Int J Epidemiol 40: 868–876. 39. Deeg DJH, Westendorp-de Serie´re M (1994) Autonomy and well-being in the aging population: report from the Longitudinal Aging Study Amsterdam, 1992– 1993. Amsterdam: VU Uitgeverij. 112 p. 40. Folstein MF, Folstein SE, McHugh PR (1975) ‘‘Mini-mental state’’: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189–198. 41. Schabereiter-Gurtner C, Selitsch B, Rotter M, Hirschl A, Willinger B (2007) Development of novel real-time PCR assays for detection and differentiation of eleven medically important Aspergillus and Candida species in clinical specimens. J Clin Microbiol 45: 906–914. 42. Nadkarni MA, Martin FE, Jacques NA, Hunter N (2002) Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiol 148: 257–266. 43. Watzinger F, Suda M, Preuner S, Baumgartinger R, Ebner K, et al. (2004) Real- time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients. J Clin Microbiol 42: 5189– 5198. 44. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, et al. (2010) QIIME allows analysis of high-throughput community sequencing data. Nature Meth 7: 335–336. 45. Reeder J, Knight R (2010) Rapidly denoising pyrosequencing amplicon reads by exploiting rank-abundance distributions. Nature Meth 7: 668–669. 46. Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R (2011) UCHIME improves sensitivity and speed of chimera detection. Bioinform 27: 2194–2200. 47. Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinform 26: 2460–2461. 48. Cole JR, Wang Q, Cardenas E, Fish J, Chai B, et al. (2009) The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucl Acids Res 37: D141–145. 49. Pruesse E, Quast C, Knittel K, Fuchs BM, Ludwig W, et al. (2007) SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucl Acids Res 35: 7188–7196. 50. Brandt BW, Bonder MJ, Huse SM, Zaura E (2012) Taxman: A server to trim rRNA reference databases and inspect taxonomic coverage. Nucleic Acids Res 40: W82–W87. doi: 10.1093/nar/gks418. 51. Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, et al. (2010) PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinform 26: 266–267. 52. Price MN, Dehal PS, Arkin AP (2010) FastTree 2– Approximately maximum- likelihood trees for large alignments. PLoS ONE 5: e9490. 53. Hammer O, Harper DAT, Ryan PD (2001) PAST: Paleontological statistics software package for education and data analysis. Palaeontol Electr 4: 1–9. 54. Lozupone CA, Hamady M, Kelley ST, Knight R (2007) Quantitative and qualitative {beta} diversity measures lead to different insights into factors that structure microbial communities. Appl Environ Microbiol 73: 1576–1585. PLOS ONE | www.plosone.org 8 August 2012 | Volume 7 | Issue 8 | e42770