Acquiring and maintaining a normal oral microbiome: current perspective

PERSPECTIVE ARTICLE published: 26 June 2014 doi: 10.3389/fcimb.2014.00085 CELLULAR AND INFECTION MICROBIOLOGY Acquiring and maintaining a normal oral microbiome: current perspective Egija Zaura 1*, Elena A. Nicu 2 , Bastiaan P. Krom 1 and Bart J. F. Keijser 3,4 1 Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, Amsterdam, Netherlands Department of Periodontology, Academic Centre for Dentistry Amsterdam, Amsterdam, Netherlands 3 Microbiology and Systems Biology, TNO Earth, Environmental and Life Sciences, Zeist, Netherlands 4 Top Institute Food and Nutrition, Wageningen, Netherlands 2 Edited by: Alex Mira, Center for Advanced Research in Public Health, Spain Reviewed by: Sung Ouk Kim, University of Western Ontario, Canada Elizabeth B. Norton, Tulane University, USA *Correspondence: Egija Zaura, Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, Gustav Mahlerlaan 3004, 1081LA Amsterdam, Netherlands e-mail: The oral microbiota survives daily physical and chemical perturbations from the intake of food and personal hygiene measures, resulting in a long-term stable microbiome. Biological properties that confer stability in the microbiome are important for the prevention of dysbiosis—a microbial shift toward a disease, e.g., periodontitis or caries. Although processes that underlie oral diseases have been studied extensively, processes involved in maintaining of a normal, healthy microbiome are poorly understood. In this review we present our hypothesis on how a healthy oral microbiome is acquired and maintained. We introduce our view on the prenatal development of tolerance for the normal oral microbiome: we propose that development of fetal tolerance toward the microbiome of the mother during pregnancy is the major factor for a successful acquisition of a normal microbiome. We describe the processes that influence the establishment of such microbiome, followed by our perspective on the process of sustaining a healthy oral microbiome. We divide microbiome-maintenance factors into host-derived and microbe-derived, while focusing on the host. Finally, we highlight the need and directions for future research. Keywords: oral microbiome, placenta, tolerance, mucosal immunity, stability, colonization resistance INTRODUCTION The oral microbiota needs to cope with daily physical and chemical perturbations from the intake of food and personal hygiene measures. These include fluctuations in temperature, pH, antimicrobial and dietary components, and mechanical sheer forces from brushing and mastication. Intriguingly, a long-term stable microbiome is maintained in the oral cavity, as demonstrated by Rasiah and colleagues by following an individual saliva donor over a period of 7 years (Rasiah et al., 2005). Recent data from the NIH Human Microbiome Project (HMP) revealed that the oral microbiome has the largest core of commonly shared microbes among unrelated individuals compared to other habitats such as gut or skin (Costello et al., 2009; Li et al., 2013; Zhou et al., 2013). A key question is what governs the stability of the oral microbiome in health? Biological properties that confer stability in the microbiome are important for the prevention of dysbiosis—a microbial shift toward a disease, e.g., periodontitis or caries and sustaining general health (for review see Wade, 2013). Although processes that underlie oral diseases have been studied extensively (Bartold and Van Dyke, 2013; Bradshaw and Lynch, 2013; Nyvad et al., 2013; Belibasakis, 2014), processes behind the maintaining of a normal microbiome are poorly understood. In this review we present our hypothesis on how a healthy oral microbiome is acquired and maintained. We start by defining what constitutes a normal oral microbiome. Then we Frontiers in Cellular and Infection Microbiology present our hypothesis on the mechanisms for acquiring a stable normal microbiome. Finally, we discuss some of the mechanisms involved in maintaining such a microbiome and highlight the directions for possible further research. WHAT CONSTITUTES NORMAL ORAL MICROBIOME? The human oral cavity is colonized by a wide range of microorganisms. Besides bacteria and fungi, Archaea, viruses and protozoa form a part of a normal microbiome (Wade, 2013). Current reports on a normal oral microbiome however are limited to the “bacteriome” (subsequently referred to as “microbiome”) and very limited reports on the mycobiome— fungal microbiome (Ghannoum et al., 2010; Dupuy et al., 2014; Mukherjee et al., 2014). Current knowledge on the role of fungi as part of a healthy oral microbiome has been recently reviewed and is therefore not further discussed here (Krom et al., 2014). The microbiome has been studied in great detail and phylogenetic information of oral bacteria is gathered in databases dedicated to oral cavity (Palmer, 2014). The HMP assessed microbiome composition of nine intraoral sites (buccal mucosa, hard palate, keratinized gingiva, palatine tonsils, saliva, sub- and supragingival plaque, throat and tongue dorsum) from about 200 subjects and found 185–355 genera, belonging to 13–19 bacterial phyla (Zhou et al., 2013). An individual sample (i.e., from a single site of a single volunteer) contained sequences classified to 20–50 genera from 6 to 9 phyla. Table 1 summarizes the high abundance www.frontiersin.org June 2014 | Volume 4 | Article 85 | 1 Zaura et al. Acquiring and maintaining a normal oral microbiome Table 1 | The core bacterial taxa in the oral cavity from over 200 healthy individuals participating in HMP (Li et al., 2013). Sample type High abundance core genera in >75% samples at >10% abundance Other major core genera in >80% samples at >1% abundance Minor core genera in >50% samples Buccal mucosa Streptococcus (2) Uncl. Pasteurellaceae (16, 19) Gemella (11) Atopobium Uncl. Prevotellaceae Uncl. Bacilli Catonella Hard palate Streptococcus (2, 6) Uncl. Pasteurellaceae (16) Veillonella (4) Prevotella (10) Uncl. Lactobacillales (13) Gemella (11) Mogibacterium Catonella Keratinized gingiva Streptococcus (2) Uncl. Pasteurellaceae (19) Uncl. Bacilli Palatine tonsils Streptococcus (2, 6) Veillonella (4) Prevotella (10) Fusobacterium (9) Uncl. Pasteurellaceae (16) Mogibacterium Uncl. Firmicutes Saliva Prevotella (10) Streptococcus (2, 6) Veillonella (4) Uncl. Pasteurellaceae (16) Fusobacterium (9) Porphyromonas (7) Neisseria (−) Uncl. Actinomycetales Tannerella Kingella Subgingival plaque Streptococcus (2) Fusobacterium (9) Capnocytophaga (−) Prevotella (−) Corynebacterium (−) Uncl. Pasteurellaceae (−) Uncl. Firmicutes Supragingival plaque Streptococcus (2) Capnocytophaga (−) Corynebacterium (15) Uncl. Pasteurellaceae (−) Uncl. Neisseriaceae (21) Fusobacterium (9) Uncl. Betaproteobacteria Throat Streptococcus (2, 6) Veillonella (4) Prevotella (10) Uncl. Pasteurellaceae (16) Actinomyces (−) Fusobacterium (9) Uncl. Lachnospiraceae (−) Mogibacterium Un (...truncated)