applied sciences Review Oral Microbiome and Host Health: Review on Current Advances in Genome-Wide Analysis Young-Dan Cho, Kyoung-Hwa Kim , Yong-Moo Lee, Young Ku and Yang-Jo Seol * Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul 03080, Korea; [email protected] (Y.-D.C.); [email protected] (K.-H.K.); [email protected] (Y.-M.L.); [email protected] (Y.K.) * Correspondence: [email protected]; Tel.: +82-2-2072-0308 Abstract: The oral microbiome is an important part of the human microbiome. The oral cavity has the second largest microbiota after the intestines, and its open structure creates a special environment. With the development of technology such as next-generation sequencing and bioinformatics, exten- sive in-depth microbiome studies have become possible. They can also be applied in the clinical field in terms of diagnosis and treatment. Many microbiome studies have been performed on oral and systemic diseases, showing a close association between the two. Understanding the oral microbiome and host interaction is expected to provide future directions to explore the functional and metabolic changes in diseases, and to uncover the molecular mechanisms for drug development and treatment that facilitate personalized medicine. The aim of this review was to provide comprehension regarding research trends in oral microbiome studies and establish the link between oral microbiomes and systemic diseases based on the latest technique of genome-wide analysis. Keywords: oral microbiome; oral disease; systemic disease; genome-wide analysis; personal- Citation: Cho, Y.-D.; Kim, K.-H.; Lee, ized medicine Y.-M.; Ku, Y.; Seol, Y.-J. Oral Microbiome and Host Health: Review on Current Advances in Genome-Wide Analysis. Appl. Sci. 1. Introduction 2021, 11, 4050. https://doi.org/ The human oral cavity is the second largest microbial habitat comprising fungi, bac- 10.3390/app11094050 teria, and viruses, after the intestines, and has a special niche consisting of soft tissue of the gingiva and oral mucosa and the hard tissue of the teeth [1]. Although the oral cavity Academic Editor: Yoshiaki Nomura and intestines are a distance apart, they are connected and show a marvelous diversity of microorganisms. The oral microbiome refers to the collective genetic materials of oral Received: 30 March 2021 microorganisms. The microorganisms in the oral cavity are referred to as oral microbiota, Accepted: 27 April 2021 Published: 29 April 2021 oral microflora, and oral microbiome [2]. Microorganisms coexist in our bodies and live through symbiosis, dysbiosis, and pathogenic relations. The microbiome not only refers to Publisher’s Note: MDPI stays neutral the microorganisms involved, but also includes areas of activity that result in the formation with regard to jurisdictional claims in of specific ecological niches. Significant changes in the local environment can disrupt the published maps and institutional affil- microbe–microbe interaction, which can alter the host–microbe equilibrium, increasing iations. the risk of disease [3]. The oral cavity is the most accessible habitat for studying the relationship between the host and microorganisms. Different oral structures such as the teeth, the gingiva, the palate, the cheek, and the lips are colonized by distinct microbial communities, and the surfaces of the oral cavity are covered with bacterial biofilm [4]. The special environment of the oral cavity, with its stable pH of 6.5–7.0 of saliva, moisture, Copyright: © 2021 by the authors. ◦ Licensee MDPI, Basel, Switzerland. and its temperature of an average of 37 C, creates the favorable conditions necessary for This article is an open access article the growth of microorganisms [5]. For this reason, various kinds of microorganisms are distributed under the terms and well distributed in the mouth. The oral cavity is one of the best-studied microbiomes to conditions of the Creative Commons date, with research focusing on its role as a part of human microbiome development and Attribution (CC BY) license (https:// how it influences systemic health and disease. About 700 species of prokaryotes have been creativecommons.org/licenses/by/ identified [6], and 392 taxa with at least one reference genome exist [7]. In the near future, 4.0/). the advances in our understanding of oral microbiomes may change our way of life through Appl. Sci. 2021, 11, 4050. https://doi.org/10.3390/app11094050 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, x FOR PEER REVIEW 2 of 16 the advances in our understanding of oral microbiomes may change our way of life through in-depth principles of oral biology and novel therapeutics. In this review, we pro- vide a general understanding of the oral microbiome, establish the link between oral mi- crobiomes and general health based on a genome-wide analysis through the latest tech- Appl. Sci. 2021, 11, 4050 2 of 16 nique, and discuss the perspective and future directions for both oral and systemic health. 2. Paradigm Shift: Microorganisms to Microbiomes in-depth principles of oral biology and novel therapeutics. In this review, we provide a The term “microorganism”general understanding simply of therefers oral to microbiome, very small establish living the things link between such as oral archaea, microbiomes bacteria, protists, fungi,and general and viruses, health based while on a“microbiome” genome-wide analysis is a collective through theand latest comprehen- technique, and sive term for microorganisms.discuss the perspective The community and future of directions microbial for both residents oral and is systemic referred health. to as the microbiome, and recent2. Paradigm research Shift: on Microorganisms microbiomes to has Microbiomes demonstrated an important role of the communities of microorganThe term “microorganism”isms in human simply homeostasis refers to very(Figure small 1A) living [8]. things The term such as“mi- archaea, crobiome” was coinedbacteria, by protists,Joshua fungi, Lederberg, and viruses, a Nobel while “microbiome”Prize laureate, is a collective “to signify and comprehensivethe eco- logical communityterm of commensal, for microorganisms. symbiotic, The community and pathogenic of microbial microorganisms residents is referred that to liter- as the mi- crobiome, and recent research on microbiomes has demonstrated an important role of the ally share our bodycommunities space and of have microorganisms been all but in human ignored homeostasis as determinants (Figure1A) [of8]. health The term and “micro- disease”, [9]. As a collectionbiome” was of coined information, by Joshua the Lederberg, microbiome a Nobel includes Prize laureate, the microorganisms’ “to signify the ecological genomic data, structuralcommunity elements, of commensal, metabolites symbiotic,, and and environmental pathogenic microorganisms conditions that(Figure literally 1A) share [10]. With the emergenceour body spaceof new and havetechnolo been allgy, but including ignored as determinantsnext-generation of health sequencing and disease” [9]. (NGS), and in-depthAs information, a collection of information, such as sequence the microbiome profiles includes of microbial the microorganisms’ communities, genomic nu- data, structural elements, metabolites, and environmental conditions (Figure1A) [10]. With the merous insights onemergence the relation of new between technology, the including human next-generation microbiome sequencingand disease (NGS), have and been in-depth obtained [11]. information, such as sequence profiles of microbial communities, numerous insights on the relation between the human microbiome and disease have been obtained [11]. Figure 1. From microorganism to microbiome; a paradigm shift with advanced technology. (A) The term, microbiome, refersFigure not only 1. From to the microorganismsmicroorganism but to also microbiome; to their theatre a paradigm of activity. ( Bshift) Timeline with ofadvanced microbiome technology. research. (A) The term, microbiome, refers not only to the microorganisms but also to their theatre of activity. In the 1670s, the study of human microbiology was initiated with the invention of (B) Timeline of microbiome research. the microscope, and the consequent observation of bacteria in pond water and dental plaque, by Antoni Philips van Leeuwenhoek [12,13] (Figure1B). He was the first to observe In the 1670s, themicroorganisms study of human and determine microbiology their sizes. was Afterinitiated that revolutionary with the invention invention, of a the culture- microscope, and thebased consequent method that observation is dependent of onbacteria the growth in pond of viable water and and culturable dental microbesplaque, was by Antoni Philips vanintroduced Leeuwenhoek to identify [12,13] microbes (Figure with biochemical 1B). He was subtyping the first in theto observe 1800s [14 mi-]. After croorganisms and thedetermine 1980s, the their emergence sizes. of Afte newr technology, that revolutionary such as DNA invention, sequencing, a whichculture- enables acquisition of more than 1 trillion sequences of genetic information, provided a powerful based method thatunculturable is dependent method on the for growth understanding of viable human and health culturable and disease microbes [15]. Basedwas in- on this troduced to identifyadvance microbes in sequencing with bioche technology,mical the subtyping Human Genome in the Project 1800s (HGP) [14]. was After started the in 1990 1980s, the emergenceand