*Human Oral Microbiome Database (HOMD)*

The main purpose of HMP was to produce 1000 microbial reference genomes, including about 300 among the oral microbes [53]. As a national resource project, the data of HMP were released rapidly, and a Data Analysis and Coordinating Center was established. Additionally, comprehensive analyses of body site-specific data from HMP1, including oral, gut, skin, and vagina data, and taxonomic classification of newly identified microbes, were needed. The HOMD is the first oral-specific public database providing the scientific community with comprehensive information on oral microbiome species [54]. The HOMD database and web-based interface were set up under the Foundation for the Oral Microbiome and Metagenome from the National Institute of Dental and Craniofacial Research, and were organized based on taxonomic classifications, which were identified based on 16S rRNA sequencing data [2,54]. The named oral species and taxa identified in 16S rRNA sequencing were placed dependent on their 16S rRNA types and their unique human oral taxon (HOT) number. The HOT interconnects phylotypes, phenotypes, and the genomic, bibliographic, and clinical information of each taxon.

#### **7. Host–Oral Microbiome Interactions in Health**

The oral cavity has evolved to improve oral health and fosters highly personalized microbiomes that exist dynamically in balance with the host. The symbiotic relationship

between host and microbiome maintains microbial homeostasis; however, dysbiosis, a breakdown of the microbial homeostasis, induces oral disease and increases the risk for systemic diseases. The inseparable relationship between the host and microbiome is formed over a long time by facing various changes that force the adaptation of the oral microbiome to the new environment [55]. A bidirectional relation is characterized by the microbe providing the host with abilities it lacks alone, while the host provides an appropriate environment for microbial growth [56]. The host factors can positively affect the microbiome, making balance and diversity between the species, thus inducing symbiosis and an absence of pathology. On the contrary, the host can also create a negative influence [56,57]. This co-evolution between the host and microbiome succeeded in achieving a complex biological process in which the existence of independent entities would be impossible. The mutual benefits from the maintenance of a balanced host–oral microbiome ecology can be distorted to induce a shift from a healthy and symbiotic relation to a pathologic and dysbiotic one [58,59]. This distortion can result from changes in the oral microbiome as well as in the host [60]. Even though the host and the microbiome are equivalent factors, early studies have focused on finding the pathological oral microbiome, and the role of the host in maintaining a healthy oral microbiome was overlooked. Based on this, recent research trends have moved to focus on the host factors and combined the role of host–oral microbiome in the development of a healthy and balanced oral ecology, and extended to systemic disease and oral disease [61,62]. The host factors are largely classified into two, intrinsic and extrinsic, factors (Table 1). The oral microbiome is associated with a variety of oral diseases. Recently, there has been growing evidence that the oral microbiome is closely related to physical conditions, with many intermediate host factors [63].

**Table 1.** Host Factors to Modulate the Oral Microbiome.

