## 2 The Influence of Different Factors on Oral Microbiome  
### Age, Sex, Race/Ethnicity and Genetic Makeup  
Age, sex, and race/ethnicity are demographic factors that significantly influence the composition and diversity of the oral microbiome. Aging is associated with changes in microbial diversity, often leading to a decrease in beneficial microbial populations and an increase in pathogenic species [37]. This shift may be due to age-related changes in immune function, oral hygiene practices, and salivary composition. For instance, studies have shown that the elderly tend to have higher levels of periodontal pathogens compared to younger individuals, which may contribute to chronic inflammation and a higher susceptibility to OPMD and OSCC [38; 39; 40; 41]. Sex differences can also impact the oral microbiome, potentially through hormonal regulation. Hormones such as estrogen and testosterone can influence the microbial environment, leading to variations in microbiome composition between males and females [42]. For example, hormonal fluctuations during puberty, menstruation, pregnancy, and menopause can affect the balance of microbial communities in the oral cavity, potentially influencing the development of OPMD and OSCC [43; 44]. Ethnic variations in diet and genetics further contribute to differences in the oral microbiome. Dietary habits, which vary widely across different ethnic groups, play a crucial role in shaping the microbiome. For instance, diets rich in carbohydrates and sugars can promote the growth of cariogenic bacteria, whereas diets high in fruits and vegetables support a more diverse and balanced microbial community [45]. Moreover, these differences may affect susceptibility to OPMD and OSCC. For example, certain dietary habits prevalent in specific ethnic groups can influence the prevalence of oral pathogens associated with carcinogenesis [41]. Genetic factors also influence the oral microbiome by affecting host immune responses and susceptibility to microbial colonization. Studies have demonstrated significant differences in the oral microbiomes of different racial and ethnic groups, which may be linked to both genetic predispositions and cultural practices [46; 47]. Genetic factors play a critical role in determining the composition of the oral microbiome, influencing individual susceptibility to microbiome alterations and disease development [46; 48]. The interplay between host genetics and microbial communities can shape the oral environment, affecting how the microbiome responds to various external and internal factors. The human genome encodes for proteins that influence the immune system, mucosal surfaces, and salivary composition, all of which can impact the oral microbiome. Genetic variations, such as single nucleotide polymorphisms (SNPs), can affect immune responses and the ability to control microbial populations. For example, genetic polymorphisms in the _IL-1_ gene cluster have been associated with increased inflammatory responses and a higher risk of periodontitis [49]. Host genetics also play a role in the production and composition of saliva, which is essential for maintaining oral health. Saliva contains antimicrobial proteins, enzymes, and immunoglobulins that help regulate the microbial communities in the oral cavity. Genetic differences in salivary protein expression can influence the oral microbiome composition, potentially affecting the prevalence and severity of oral diseases [50]. Furthermore, studies have shown that genetic makeup can determine the baseline composition of the oral microbiome, with specific bacterial taxa being more prevalent in certain genetic backgrounds. For instance, twin studies have revealed that the oral microbiomes of monozygotic twins are more similar to each other than to those of dizygotic twins, indicating a strong genetic component in microbiome composition [51]. These findings suggest that individuals with certain genetic backgrounds may be predisposed to specific microbial profiles, which could influence their risk of developing oral diseases.