Comparison of the main pathogenic microorganisms of various common oral diseases in children and adults

The microorganisms in the human body gradually change and maintain a dynamic balance with the development of physiology and pathology. Oral microbiota is one of the most important microbiota in human body. It is not only closely related to the occurrence and development of oral diseases, but also plays an important role in the overall health. In childhood, the population of oral microorganisms is relatively small, but with the growth of age and tooth development, the species and quantity of oral microorganisms are gradually increasing. Different oral diseases also have their corresponding main microorganisms, and these dominant microorganisms change at different stages of the disease. In this review, we summarized and compared the main pathogenic microorganisms of several common oral diseases in children and adults. In addition, the possible association and difference between adults and children of the main pathogenic microorganisms in different stages of the same or different diseases are also discussed in order to provide research data for the development and diagnosis of common oral diseases in children and adults.

Since the birth of each newborn, bacterial communities begin to colonize the human body. 1,26][7][8] At the beginning, in edentulous stage, the main location of oral flora is at the surface of oral mucosa and 3 the main bacteria are gram-positive facultative bacteria, followed by gram-negative anaerobic bacteria. 6,9Streptococcus salivarius is the most commonly isolated bacteria in the oral mucosa of newborn infants because it has better adhesion with buccal mucosa and tongue 1 ; it keeps a relatively stable growth in the first 3 months of the newborn but begins to decrease after 3 months, which is believed to be related to the eruption of the first deciduous tooth in the mouth of children. 1,10At the same time, Streptococcus mutans begin to accelerate its colonization, and it is due to the greater adhesion of S. mutans to the tooth surface compared with other bacteria in the mouth. 8The proportion of S. mutans, Pasteurellaceae, and Enterobacteriaceae in primary dentition stage is higher than that in other dentition stages. 8After the eruption of the last deciduous tooth, the operational taxonomic units of bacteria that can be detected in the mouth have reached 550. 4 The proportion of Pasteurellaceae and Carnobacteriaceae in mixed dentition stage is higher. 8In the period of permanent dentition, there are 10,000 microbial system types in dental plaque alone, which is far more than the more than 700 oral microbial system types detected by traditional methods. 11stly, it is worth noting that fungi and viruses are also present in the oral cavity of a newborn baby after birth, and these fungi and viruses may also be occasional causative factors in certain contexts, such as congenital immunodeficiency.Candida is the most frequently detected fungus; other fungi such as Cladosporium, Aureobasidium, Saccharomycetales, Aspergillus, Fusarium, and Cryptococcus also exist at the same time. 12- 14 [17][18][19][20] Therefore, the oral microbiota changes with time and maintains a dynamic balance.The oral microbiota in different periods is different, which also conforms to the view of ecological succession. 6,21Understanding the differences and changes of oral microbiota has long been considered as a very important aspect for disease prediction and diagnosis.However, nowadays, research on the main microorganisms of common oral diseases in children and adults mainly focuses on the comparison of oral flora between parents and children with the same disease or the influence of one party's illness on the other party's oral flora or other physical conditions.This article believes that by comparing the main microorganisms of common oral diseases in children and adults, new discoveries may be made about the role in children's caries.Majda Dzidic et al. compared the bacteria in saliva of children with caries and children without caries from 3 months to 7 years old by high-throughput sequencing.The experimental results showed that after 2 years of age, caries affected and caries-free children had significantly different bacterial colonization patterns, but before 2 years of age, the difference was not obvious, and before 7 years of age, the incidence rate of caries was not significantly related to bacterial diversity or bacterial abundance.After 7 years of age, compared with children without dental caries, children with dental caries have higher levels of S. mutans and Streptococcus cristatus and lower level of Streptococcus dentisani. 5Jørn A. Aas et al. believed that there were more kinds of health-related bacteria isolated from the plaque of permanent teeth than that of deciduous teeth, but the main bacteria in deciduous teeth were still included in the plaque of permanent teeth.As for pathogenic bacteria, compared with deciduous teeth, there is a significantly greater overall diversity of bacteria related to permanent teeth caries.The distribution of bacteria at the beginning of caries (i.e., intact enamel and white plaque on enamel surface) is also more obvious and complex than that in the identified caries.At the same time, the main bacteria of adults and children are different in different stages and parts of caries development.When the caries was confined to the enamel and superficial dentin, high levels of S. parasanguinis and S. salivarius were observed in the dental plaque of both permanent and deciduous teeth, but high levels of Corynebacterium sp.clone AK153, and Actinomyces gerencseriae were detected in deciduous dentition and high levels of Leptotrichia sp.clone GT018, Campylobacter gracilis, and Selenomonas sp.clone EY04 were detected in permanent dentition.When the caries progressed to the deep dentine layer, the microbial community was dominated by S. mutans, Lactobacillus spp., Propionibacterium sp.strain FMA5, Atopobium genomospecies C1 (permanent teeth), and Bifidobacterium spp.(deciduous teeth). 32 addition, it should not be ignored that early childhood caries (ECC) is a kind of caries that develops rapidly and has a wide range, especially in children under 6 years of age.The bacteria contained in the oral cavity of young children with ECC may be different from pathogenic bacteria of adult caries.The study found that children with severe early childhood caries had elevated levels of streptococci (especially Streptococcus mutans), Leptosella, Prevoella, oral bacillus, bifidobacteria, Porphyromonas and Salmonella in the mouth compared with children without dental caries. 33Kanasi et al. compared the bacteria at different positions in oral cavity of children with EEC and caries-free children and concluded that the related species of EEC mainly include: S. mutans, S. mutans combined with Streptococcus sobrinus, Lactobacillus vaginalis, Staphylococcus intermedius, Lactobacillus fermentum, Lactobacillus gasseri, Actinomyces odontolyticus, Actinomyces israelii, and Veillonella parvula.Among them, the pathogenic rate of S. mutans combined with S. sobrinus to EEC is higher than that of single S. mutans, and among the EEC detected by non S. mutans, it is S. intermedius that is more relevant.Prevotella nigrescens is the only species that is significantly associated with caries.Furthermore, the detected bacteria related to caries have a much higher content in dental plaque than in tongue and saliva, but it has little relationship with the tooth position. 346][37][38][39][40] The role of S. mutans in the development of caries may be related to its characteristics of acid production and acid resistance, and it can provide biofilm matrix for other cariogenic bacteria when the biofilm matures, thus, protecting the acidic environment where acid production and acid bacteria grow. 36Moreover, other microorganisms such as human herpesvirus type 4 (Epstein-Barr virus [EBV]) and Candida albicans were confirmed to have higher levels in EEC than subjects with common caries or without caries 38,41,42 (Table 1).
Therefore, during the occurrence and development of caries, the pathogenic microorganisms of caries in adults and children are different.Adults mainly include salivary streptococcus, blood streptococcus, etc. S. mutans plays an important role in the development of caries in children.The microbial diversity of adults is higher than that of children.

| Pulpal disease
Pulp disease is a general term for dental pulp tissue diseases.This section mainly introduces the microorganisms in the common diseases of pulpitis and pulp necrosis caused by infection and is limited to root canal.Bacteria are the most important pathogenic factor of dental pulp disease, mainly including facultative anaerobes and obligate anaerobes.Due to the characteristics of tooth structure, bacterial infection mainly comes from tooth defect, periodontal infection, and blood infection, among which microorganisms play a vital role.Many studies have shown that significant changes have taken place in the microbiota in the root canal of dental pulp infection, and the richness of dominant bacteria and species in different infection stages are also different. 43,44Dental caries is an important cause of pulp infection.In the severe caries stage, when the decay is very close to the pulp, bacteria can infect the pulp through the dentinal tubules. 45With the further development of the disease, the symptoms of reducible pulpitis, irreducible pulpitis, and pulp necrosis appear immediately.
The content of anaerobes is less, and facultative anaerobes are more dominant than strict anaerobes. 491][52] Similarly, they are dominated by facultative anaerobes (Table 2).However, at present, the research objects of dental pulp infection bacteria mainly focus on individuals suffering from periapical infection, especially deciduous teeth pulpitis.Due to the difficulty in obtaining materials, the relevant research results are even rarer.Therefore, for the infection that has not developed to the stage of periapical periodontitis, more research is needed to detect the dominant bacteria and community characteristics.

| Periapical periodontitis
With further development of the lesion, microorganisms in the necrotic pulp may spread to and around the root apex through special structures such as apical foramen, dentinal tubules, lateral root canals, apical furcations, and accessory root canals, leading to periapical periapical Inflammation, and even periapical granuloma, apical cyst or apical abscess may occur, eventually leading to tooth pain, looseness, formation of mucosa or buccal fistula and other symptoms. 53,54For nonstandard root canal therapy or root canal therapy failure, periapical periodontitis is often one of the most common sequelae.However, deciduous teeth with periapical periodontitis may have some impact on the development or eruption of subsequent permanent teeth, such as the occurrence of Turner teeth. 55,56The bacteria in periapical periodontitis are slightly different from those in pulpitis.
The most common microorganisms isolated from adult periapical periodontitis are mainly anaerobic bacteria.Wayman et al. successfully isolated Staphylococcus epidermidis, Fusobacterium nucleatum, Propionibacterium acnes, Peptostreptococcus micros, and Bacteroides gracilis from periapical tissues. 57Combined with other studies, it can be concluded that the bacteria of adult periapical periodontitis are mainly Actinomycetes, Fusobacterium, and Prevotella, including C. gracilis, Porphyromonas endodontalis, Bacteroides forsythus, P. acnes, Capnocytophagagingivalis, F.nucleatum ssp.nucleatum, F. nucleatum ssp.polymorphum, Prevotella intermedia, Treponema denticola, Streptococcus constellatus, Actinomyces naeslundii, Actinobacillus actinomycetemcomitans (Aa), Eubacterium sabureum, P. micros, V. parvula, Streptococcus anginosus, Leptotrichia buccalis, Capnocytophaga sputigena, Streptococcus gordonii, Actinomyces viscosus, etc. 58,59 There are also a few research results showing that the root canals or periapical tissues of teeth with persistent infection of periapical periodontitis have also been found to contain fungi, especially C. albicans, in addition to Candida glabrata, Candida unspicua, Geotricum candium, etc. 60 EBV and human cytomegalovirus (HCMV) were also found in periapical tissues, 61,62 which suggests that viruses may also play a role in the occurrence and development of periapical periodontitis.In children's periapical periodontitis, the detection rates of Porphyromonas, T. denticola, E. faecalis, Prevotella, Fusobacterium, Peptostreptococcus, Streptococcus, Eubacterium, Lactobacillus, Campylobacter, and Bulleidia were higher.4][65] Teuta Kutllovci et al. found that the dominant bacteria group of periapical infection in children is anaerobic bacteria, mainly including Actinomyces mayeri, A. naeslundi, Actinomyces odontoliticus, Fusobacterium, Veillonella, and Lactobacillus.In acute infection, the detection rate of Actinomycetes in deciduous teeth is higher than that in chronic infection group, while the proportion of Fusobacterium in deciduous teeth is not closely related to the acute and chronic stages, and its content is always higher than that in permanent teeth group (Table 3). 65

| Periodontal disease
The most common forms of human periodontal disease are gingivitis and periodontitis.Gingivitis is an inflammatory disease that is limited to gingival tissue without causing attachment loss and alveolar bone absorption and is reversible.The bacterial flora related to adult gingivitis mainly includes TM7, Leptotrichia, Selenomonas, Streptococcus, Veillonella, Prevotella, Neisseria spp., Hafnia alvei, C. albicans, Lautropia, Pseudomonas aeruginosa, and Haemophilus. 66,67riodontitis is a chronic inflammatory disease.Its main symptoms include gingival redness and bleeding, alveolar bone absorption, and tooth mobility.The damage to tissues caused by periodontitis is irreversible.Its main cause is the presence of specific bacteria in the subgingival plaque biofilm and the change of the flora. 68,69For this reason, it is of great significance to determine the dominant flora of periodontitis for the understanding and treatment of this disease.So far, Aggregatibacter actinomycetem, Tannerella forsythensis, and Porphyromonas gingivalis are almost recognized as the main pathogens leading to the onset and development of periodontitis. 70,71The dominant bacteria in the saliva of patients with periodontitis are P. gingivalis, Ac. actinomycetemcomitans, and S. mutans. 29,72,73nner et al. compared the flora on the back of the tongue and subgingival of early adult periodontitis samples and found that T. denticola, Filifactor alocis, F. nucleatum, and P. gingivalis were related to progressive periodontitis, and the subgingival samples were more reliable than tongue samples when detecting periodontal pathogens. 74In addition, Riviere et al. found that the abundance of P. gingivalis under the gingiva of patients with early periodontitis was higher than that of healthy people, and the level of P. gingivalis in patients with gingivitis was higher than that in patients with early periodontitis. 75Colombo et al. found that subgingival flora of adult periodontitis patients had more kinds and quantities of pathogenic bacteria than that of healthy individuals, such as Parvimonas micra, C. gracilis, Tannerella forsythia, P. gingivalis, Megasphaera micronuciformis, Eubacterium nodatum, Selenomonas noxia, Leptotrichia, V. parvula, Prevotella spp., Treponema spp., Eikenella corrodens, Pseudoramibacter alactolyticus, TM7 spp.oral taxon OT 346/356, Bacteroidetes sp.OT 272/274, Solobacterium moorei, Desulfobulbus sp.OT 041, Brevundimonas diminuta, Sphaerocytophaga sp.OT 337, Shuttleworthia satelles, F. alocis, Granulicatella adiacens, Mogibacterium timidum, Veillonella atypica, and Mycoplasma salivarium. 76- 78 t has also been proved that the bacteria related to periodontal injury are mainly enterobacteria and C. albicans, Neisseria spp., P. aeruginosa, Olsenella uli, Hafnia alwei, Serratia marcescens, and F. alocis. 67wever, different from most oral anaerobes, with the growth of age, some periodontal pathogens usually do not colonize the oral cavity in the early stage, and most healthy children do not suffer from periodontitis. 79,80Therefore, the bacteriological study of periodontal disease in healthy children is still rare.Morinushi et al. found that P. gingivalis and Actinomycetes appeared as early as 3 years old in children, and their existence was related to the onset and severity of gingivitis in children. 81Sheila Cavalca Cortelli et al. detected that P. gingivalis was the most abundant bacteria in the gingival biofilm samples of 196 children with gingivitis, followed by Tannerella forsythensis, P. intermedia, Aggregatibacter actinomycetemcomitans, and Campylobacter rectum. 82P. intermedia, Eikenella corrodes, Black-pigmented Bacteroides species, Bacteroides intermedius, Ac. actinomycetemcomitans, F. nucleatum, etc. also account for a high proportion of children's gingivitis bacteria. 83In addition, Moore et al. found that F. nucleatum, Actinomyces WVa 963, Selenomonas D04, and Treponema socranskii were the main species related to the increase of gingival index scores in children and adults.Compared with adults who also suffer from gingivitis, the proportion of Leptotrichia species detected in children's dental plaque is 3 times higher, the proportion of Capnocytophaga species is 2.5 times higher, and the proportion of Selenomonas species is 2.3 times higher, but the proportion of Fusobacterium, Eubacterium, and Lactobacillus in adults is higher. 84As for children with invasive periodontitis, Aa is considered to be the main pathogenic bacteria in subgingival plaque, and the abundance of F. alocis, Tannerella, S. moorei, Parvimonas microca, and Capnocytophaga is also high. 85searchers analyzed the viruses detected in subgingival samples of patients with periodontitis and found that the levels of EBV, HCMV, and HSV-1 increased with the severity of periodontal disease, 86 and the amounts of these viruses were related to P. gingivalis, T. denticola, Fusobacterium periodonticum, and S. aureus in periodontal tissue. 87wever, there is no definite evidence that there must be a relationship between the virus and the pathogenic bacteria of periodontitis, [88][89][90] perhaps this can also become a new research hotspot.
Moreover, we see that the main microorganisms of periodontitis or gingivitis in children and adults are similar, but the proportion of dominant microorganisms is different between adults and children (Table 4).At present, most of the microbiological samples related to periodontitis are taken from saliva or subgingival plaque.There are relatively few studies on gingival crevicular fluid.Although there are quite rich studies on adult periodontitis, there are few studies on children with periodontitis, so we need to use more samples to further explore the oral dominant microorganisms of children's periodontitis.

| Oral mucosal disease
Oral mucosal disease refers to the general term of oral mucosal and soft tissue diseases.The causes of mucosal disease are complex, and most of them are related to the general and mental state.This part mainly introduces the oral microorganisms related to denture stomatitis, recurrent aphthous ulcer, and angular stomatitis.The main microorganisms of adults and children in common mucosal diseases are summarized in Table 5.

|
Denture stomatitis-Denture stomatitis is a mucosal disease in the mouth of patients wearing dentures.It mainly occurs in and near the mucosa covered by dentures.2][93] Elderly people who have lost their teeth and children who have early occlusion induction are the two main groups who use dentures.Among them, the incidence rate of denture stomatitis is also high. 92Due to poor oral hygiene or inadequate denture cleaning, biofilms quickly form on the denture surface.These biofilms are composed of candida and other bacteria, which can not only adhere to the denture surface, but also gradually spread to other parts of the mouth.So far, there are many evidences that C. albicans infection is an important factor leading to the disease, [94][95][96] but due to the diversity of oral bacterial community, more and more studies have found that there are many other kinds of microorganisms related to denture stomatitis.In healthy adults with denture stomatitis, the main microorganisms detected include C. glabrata, Candida tropicalis, Candida krusei, Candida parapsilosis, Candida dubliniensis, S. aureus, S. epidermidis, Klebsiella pneumoniae, P. aeruginosa, and Pseudomonas fluorescens. 97,98bb et al. found that the location of candida colonization is mainly on the surface of dentures.Compared with denture wearers without denture stomatitis, denture plaque is composed of basically similar flora, but the contents of Streptococcus species, Actinomyces species, and Veillonella species in denture stomatitis patients are less, and the content of Propionibacterium species and Lactobacillus species is higher. 95 most cases, the dentures worn by children are orthodontic movable appliances.Due to the long wearing time, children's self-oral cleaning is not in place and other reasons are that the children wearing dentures also often have symptoms such as swollen mucosa.0][101][102] There is a direct relationship between the use of removable orthodontic appliances and the increase of periodontal pathogens.

| Recurrent aphthous ulcer-Recurrent
aphthous ulcer is a recurrent, selflimited oral mucosal disease with complex etiology.The clinical symptoms are red or yellowish depressions on the oral mucosa, accompanied by erosion and pain.4][105] At present, the research on recurrent aphthous ulceration (RAU) related pathogens is still in a small stage, but few people believe that Streptococcus, especially S. sanguis may participate in the occurrence of RAU, and RAU may be a result of T cell-mediated reaction to S. sanguis. 106,107Some subpopulations of Prevotella, Neisseria, and Streptococcus, such as Prevotella melaninogenicus, Neisseria lactamica, Neisseria mucosa, Neisseria saprophaga, Neisseria subflava, Streptococcus viridans, S. mutans, and S. aureus, may be related to the occurrence of RAU. 108The significant increase in the number of Prevotella at the ulcer site more effectively indicates that Prevotella is closely related to RAU. 109 For Helicobacter pylori, there is still no direct evidence to prove that it is related to the occurrence and development of RAU. 110There is less research on viruses.At present, only a small number of people think that EBV is related to the epithelial cells of recurrent aphthous stomatitis before ulcer. 1115.3 | Angular stomatitis-Angular stomatitis is an infectious disease that occurs at the joint of the upper and lower lips, mainly manifested as chaps, flushing, dander or erosion.The bacteria associated with adult angular stomatitis are mainly found to be Candida albieans, C. parapsilosis, C. krusei, S. aureus, Beta aerolytic streptococci, E. coli, and other microorganisms.112,113 Microbes related to children's angular stomatitis mainly include S. aureus, Enterobacter cloacae, Staphylococcus warneri, C. tropicalis, Dermacoccus nishinomiyaensis, etc. S. aureus is the most dominant bacteria.114 K. pneumoniae, S. gordonii, Streptococcus oralis, Bordetella bronchiseptica, Streptococcus pseudoporcinus, Streptococcus agalactiae, S. salivarius, Gamella morbilorium, and other bacteria are also suspected to be related to the progress of angular stomatitis.114

| CONCLUSION
Due to the difficulty of plaque collection in clinical practice, the main microbial test samples are mainly from saliva, tongue back, dental plaque, or affected tissues.With the progress of science and technology, the identification of microorganisms has gradually changed from isolation and culture of microorganisms to DNA finger-printing, and then to the current high-throughput sequencing or mass spectrometry identification technology.The number of microorganisms detected in the mouth has increased from more than 700 to more than 10,000.Our understanding of microorganisms has also changed from simple morphology and classification to current gene, protein, or metabonomics.The relationship between microorganisms or between microorganisms and hosts is gradually becoming clear.However, there are many kinds and large quantities of microorganisms.The role of microorganisms in different environments and their impact on human diseases are still a major research focus today.In this review, the main microorganisms of adults and children in common oral diseases are collated and compared horizontally by consulting relevant literature, which may have new enlightenment for the microbial research of the same oral disease at different stages.
Therefore, we believe that the same disease has different microbial species types and abundance between adults and children, which may be related to the replacement of microbial populations during the growth and development of healthy individuals, or to the environmental changes, oral hygiene maintenance, or the mutual influence of other diseases during the growth process.First, at different stages of the same disease, the population richness and dominant species of microorganisms are different.For example, in the acute stage of periapical periodontitis of deciduous teeth, A. mayeri is the most abundant bacteria detected, and in the chronic stage, it becomes Anaerococus prvoti. 65With the development of dental caries, the number of actinomycetes decreases, and the increase of chlamydia is also a direct proof of this view. 44Secondly, the core microorganisms of the same disease are different between adults and children.Similarly, in acute periapical infection, even though the dominant bacteria in adults and children are A. mayeri, the relative number of these microorganisms detected in adults is higher than that in children.In the chronic phase, the relative number of these microorganisms detected in adults is basically lower than that in children.The dominant bacteria in adults is still A. mayeri, and in children it becomes A. prvoti. 65Thirdly, the main microbial species of children and adults identified in different diseases also have some overlap.For example, children with dental caries in young children more frequently detect subgingival species such as P. micromera, F. alocis, P. gingivalis, Prevotella nigescens, Porphyromonas intantalis, Aa, and L. buccalis.This may be related to the onset of gingivitis in children or even periodontitis in adolescence, and this part of the population may have a greater probability of periodontitis in adulthood. 34It is worth noting that the occurrence and development of these common oral diseases are not only caused by one or several microorganisms.Various microorganisms interact to form biofilms, thus, exerting their pathogenicity.The dominant microorganisms at different stages are also different, which is also affected by the original oral flora.Some bacteria were originally related to health, but due to the addition of other bacteria, it may become an opportunistic pathogen.
At present, the research on the main flora of oral diseases in adults and children is still mostly focused on the comparison of oral flora between mothers and children or the influence of mothers' illness on oral flora of children.In terms of longitudinal research, for example, there are still few studies on the main oral flora of patients with the same disease from childhood to adulthood, or on oral diseases with a high prevalence rate in the same family or region, oral flora changes of adults and children, etc.We can only summarize the main flora of children and adults with common and different oral diseases by comparing the existing research results and by trying to provide some new ideas or directions for this research.