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Proposed model showing caries lesions as the major or only source of Lactobacillus (LB) from the oral cavity to the GI tract. Left panel: Primary teeth (molar and incisor) in a caries-free child in the absence of LB. Most children harbor mutans streptococci (MS) as commensal bacteria of the oral cavity. Right Panel: 1. An early caries lesion with MS in the presence of simple carbohydrates (CHO; e.g., sucrose). Some teeth of children with severe early childhood caries (S-ECC) have retentive niches in the form of enamel hypoplasia (~EHP) as well as pits and fissures found on the occlusal and buccal surfaces of the molars. 2 . MS and other acidogenic microbes coalesce and form a retentive niche characterized by low pH and anaerobic conditions. Select species of LB from food or other humans accumulate in the retentive, low pH niche. If early caries continues to dentin, LB may be able to bind and/or degrade exposed dentinal collagen. 3. Caries has progressed due to lower pH contributed by both MS and LB. LB can dominate lesions to the exclusion of MS. 4 . LB from caries lesions spill over into the saliva and are swallowed, seeding the downstream gastrointestinal (GI) tract, including retentive sites in the low pH stomach. We hypothesize that in the absence of dental caries, the oral cavity does not harbor LB, and as a result, the downstream GI tract no longer has a source of LB except those present in food. 

Proposed model showing caries lesions as the major or only source of Lactobacillus (LB) from the oral cavity to the GI tract. Left panel: Primary teeth (molar and incisor) in a caries-free child in the absence of LB. Most children harbor mutans streptococci (MS) as commensal bacteria of the oral cavity. Right Panel: 1. An early caries lesion with MS in the presence of simple carbohydrates (CHO; e.g., sucrose). Some teeth of children with severe early childhood caries (S-ECC) have retentive niches in the form of enamel hypoplasia (~EHP) as well as pits and fissures found on the occlusal and buccal surfaces of the molars. 2 . MS and other acidogenic microbes coalesce and form a retentive niche characterized by low pH and anaerobic conditions. Select species of LB from food or other humans accumulate in the retentive, low pH niche. If early caries continues to dentin, LB may be able to bind and/or degrade exposed dentinal collagen. 3. Caries has progressed due to lower pH contributed by both MS and LB. LB can dominate lesions to the exclusion of MS. 4 . LB from caries lesions spill over into the saliva and are swallowed, seeding the downstream gastrointestinal (GI) tract, including retentive sites in the low pH stomach. We hypothesize that in the absence of dental caries, the oral cavity does not harbor LB, and as a result, the downstream GI tract no longer has a source of LB except those present in food. 

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Lactobacilli have been associated with dental caries for over a century. Here, we review the pertinent literature along with findings from our own study to formulate a working hypothesis about the natural history and role of lactobacilli. Unlike most indigenous microbes that stably colonize a host, lactobacilli appear to be planktonic, opportunisti...

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Context 1
... review supports the notion that lactobacilli colonizing the oral cavity are opportunistic invaders of precaries or existing caries lesions, rather than members of the indigenous biota that have coevolved with their human host. We propose that the colonization of the oral cavity by lactobacilli requires 3 essential conditions, as shown in Figure 2: 1) a retentive niche that allows lactobacilli to accumulate, which in turn creates 2) a low pH milieu and anaerobic environment, combined with 3) access to a ready source of carbohydrates. Two of these requirements involve niche creation by earlier colonizers, such as the MS and/or other cariogens. ...
Context 2
... and anaerobic environment, combined with 3) access to a ready source of carbohydrates. Two of these requirements involve niche creation by earlier colonizers, such as the MS and/or other cariogens. The concept that "S. mutans may be necessary for fissure caries, though not a sufficient condition" ( Burt et al. 1983) is consistent with our model (Fig. 2) because MS are present in both caries- free and caries-active sites. However, under cariogenic conditions, MS play the critical role required for the colonization of lactobacilli in the oral cavity (i.e., creating a retentive niche). MS begin colonizing teeth as they enter the oral cavity, especially fissured-primary molars and any ...

Citations

... By clarifying the antioxidant properties of saliva and their relevance to dental health, this research could inform future strategies for caries prevention. These may include dietary recommendations to enhance antioxidant intake or the development of dental products enriched with antioxidants to strengthen natural oral defense mechanisms [15][16][17][18][19]. Ultimately, this study aims to contribute to reducing the global burden of dental caries, improving children's oral health outcomes, and enhancing their quality of life. ...
... In the final step, additional bacteria, including Streptococcus mutans, adhere to these primary colonizers through cell-to-cell interactions, leading to the formation of a biofilm on the tooth surface, commonly known as dental plaque. Key contributors to dental caries include Streptococcus mutans [52], a major cariogenic bacterium that thrives in acidic environments and produces lactic acid from fermentable carbohydrates, and Lactobacillus species [53], which play a significant role in the progression of advanced lesions. The following Lactobacillus ...
... In the final step, additional bacteria, including Streptococcus mutans, adhere to these primary colonizers through cell-to-cell interactions, leading to the formation of a biofilm on the tooth surface, commonly known as dental plaque. Key contributors to dental caries include Streptococcus mutans [52], a major cariogenic bacterium that thrives in acidic environments and produces lactic acid from fermentable carbohydrates, and Lactobacillus species [53], which play a significant role in the progression of advanced lesions. The following Lactobacillus species are most commonly associated with the development of caries in both children and adults: Lactobacillus salivarius, Lactobacillus plantarum, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus rhamnosus, and Lactobacillus casei/paracasei [53]. ...
... Key contributors to dental caries include Streptococcus mutans [52], a major cariogenic bacterium that thrives in acidic environments and produces lactic acid from fermentable carbohydrates, and Lactobacillus species [53], which play a significant role in the progression of advanced lesions. The following Lactobacillus species are most commonly associated with the development of caries in both children and adults: Lactobacillus salivarius, Lactobacillus plantarum, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus rhamnosus, and Lactobacillus casei/paracasei [53]. ...
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The oral microbiome, comprising bacteria, fungi, viruses, and protozoa, is essential for maintaining both oral and systemic health. This complex ecosystem includes over 700 bacterial species, such as Streptococcus mutans, which contributes to dental caries through acid production that demineralizes tooth enamel. Fungi like Candida and pathogens such as Porphyromonas gingivalis are also significant, as they can lead to periodontal diseases through inflammation and destruction of tooth-supporting structures. Dysbiosis, or microbial imbalance, is a key factor in the development of these oral diseases. Understanding the composition and functions of the oral microbiome is vital for creating targeted therapies for these conditions. Additionally, the kynurenine pathway, which processes the amino acid tryptophan, plays a crucial role in immune regulation, neuroprotection, and inflammation. Oral bacteria can metabolize tryptophan, influencing the production of kynurenine, kynurenic acid, and quinolinic acid, thereby affecting the kynurenine system. The balance of microbial species in the oral cavity can impact tryptophan levels and its metabolites. This narrative review aims to explore the relationship between the oral microbiome, oral diseases, and the kynurenine system in relation to certain systemic diseases.
... Other strains could be associated with pathogenicity, particularly in the oral environment [28][29][30]. Indeed, a large number of lactobacilli, such as L. rhamnosus, Lacticaseibacillus casei, Lacticaseibacillus paracasei, Lactobacillus acidophilus and Lentilactobacillus buchneri, have been reported to be present in early-or late-stage dental caries [31][32][33][34]. ...
... Since polyP kinases are responsible for polyP accumulation, we explored how often they occur in Lactobacillaceae genomes of clades associated with dental caries [34]. A query of the IMG database [46] revealed that with the exception of the probiotic species L. salivarius as well as L. gasseri, Lactobacillaceae clades associated with caries have the genetic potential to accumulate polyP ( Table 1). ...
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Inorganic polyphosphates (polyPs) are energy-storing biopolymers synthesized by all three domains of life. PolyP accumulation has been well studied with respect to its role in stress response, but its role in dental disease has received less attention. Dental decay can be promoted by changes in pH as well as the chemical activity of ions such as phosphate in oral fluids at the enamel interface. Previous work has shown that the drawdown of phosphate from biofilm fluids can alter the saturation state of oral fluids to thermodynamically favour mineral dissolution. The members of the Lactobacillaceae are known to accumulate polyP and play a role in early-stage and late-stage dental caries. In this study, we examined the effects of potential metabolic inhibitors on polyP accumulation in Lacticaseibacillus rhamnosus . We observed that two inhibitors of the enzyme responsible for polyP synthesis, gallein and fluoride, inhibited polyP accumulation in a balanced medium. However, fluoride and gallein treatments amended with either glucose or lactate were found to enhance polyP accumulation. These results illustrate the potential complexity of polyP metabolism in the oral environment.
... In contrast, a significant negative correlation between commensal Granulicatella and PETG was observed 57,58 . Remarkably, the anaerobic cariogenic pathogen L. fermentum and the key biofilm-bridging species V. atypica and E. faecalis were absent from MSB ( Fig. 5h and Supplementary Table 3) 59 . In summary, MSB demonstrated a highly reduced preference for pathogenic species; therefore, it could maintain a cleaner aligner during the orthodontic treatment which lasts several months. ...
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Medical plastic-appliance-based healthcare services, especially in dentistry, generate tremendous amounts of plastic waste. Given the physiological features of our mouth, it is desirable to substitute dental care plastics with viscoelastic and antimicrobial bioplastics. Herein, we develop a medical-grade and sustainable bioplastic that is viscoelastic enough to align the tooth positions, resists microbial contamination, and exhibits recyclable life cycles. In particular, we devise a molecular template involving entanglement-inducing and antimicrobial groups and prepare a silk fibroin-based dental care bioplastic. The generated compactly entangled structure endows great flexibility, toughness, and viscoelasticity. Therefore, a satisfactory orthodontic outcome is accomplished, as demonstrated by the progressive alignment of male rabbit incisors within the 2.5 mm range. Moreover, the prepared bioplastic exhibits resistance to pathogenic colonization of intraoral microbes such as Streptococcaceae and Veillonellaceae. Because the disentanglement of entangled domains enables selective separation and extraction of the components, the bioplastic can be recycled into a mechanically identical one. The proposed medical-grade and sustainable bioplastic could potentially contribute to a green healthcare future.
... As demonstrated in previous researches, bacterial species, including Kingella oralis, Rothia dentocariosa, and Gemella sp. may elevate the risk for caries development [17][18][19]. Furthermore, various species of Lactobacillus have been reported to exhibit a complex and diverse manifestation in the advancing front of dentinal carious lesions, demonstrating a strong correlation with progression of dentine caries, such as L. salivarius, L. gasseri, L. fermentum, and L. casei [20][21][22]. ...
... Notably, the relative abundance was similar between group CA and group RA at T 1 , indicating that both clear aligners and traditional removable appliances elevated caries risks, and the magnitude of increased caries risk between the two groups was similar at microbial level. A significant presence of Lactobacillus species, including L. gasseri, L. salivarius, L. plantarum, L. acidophilus, and L. panis has been consistently detected in saliva and caries lesions of patients with dental caries [20,22,36,49]. In the present study, we found that L. salivarius was the prominent Lactobacillus species in supragingival plaque from group CA, while L. gasseri was the most abundant Lactobacillus species in supragingival plaque of group RA and saliva of group CA, as indicated by LEfSe analysis. ...
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Background This prospective study aims to investigate the comparative effects of clear aligners (CA) and traditional removable appliances (RA) on the cariogenic risk of patients in mixed dentition, focusing on the oral microbiome. Methods 25 children were included and assigned into CA and RA groups. Supragingival plaque and saliva samples were collected, and clinical parameters including Decay-missing-filled teeth index (DMFT), Plaque Index (PI) and Gorelick Index (GI) were recorded before treatment (T0) and after 6-month follow-up (T1). DNA was extracted from supragingival plaque and saliva and analyzed via 16S rDNA gene sequencing. Results Clinical parameters showed no statistically significant difference between groups at each time point or within group over time (p > 0.05). In both RA and CA groups, saliva exhibited significantly higher alpha diversity compared to supragingival plaque at T1, as indicated by the significantly higher Chao1 and Shannon indexes (p < 0.05). Regarding beta diversity, significant difference was observed in saliva and supragingival plaque samples between T0 and T1 within group RA (p < 0.05, Adonis), whereas no such significance was noted in the CA group (p > 0.05, Adonis). At the genus level, Lactobacillus exhibited a statistically significant increase in saliva and supragingival plaque of group RA from T0 to T1 (p < 0.05), and an increasing trend in the group CA without statistical significance (p > 0.05). At T1, Lactobacillus levels were comparable between groups, whereas species-level analysis revealed distinct cariogenic species. Conclusion Both clear aligners and traditional removable appliances resulted in elevated cariogenic risk of patients in mixed dentition at the microbial level. Distinct alterations in cariogenic species were observed to be induced by various orthodontic appliances.
... S. agalactiae primarily affects infants, potentially causing severe conditions like meningitis and sepsis, and poses risks to the elderly and immunocompromised individuals [8,11,13]. Additionally, viridans group members, such as Streptococcus mutans, contribute to dental cavities by producing acid from sugar breakdown, illustrating the broad impact of the streptococcal species on human health across various domains [8,14]. ...
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Streptococcus species represent a significant global cause of meningitis, leading to brain damage through bacterial virulence factors and the host inflammatory response. Upon entering the central nervous system (CNS), excessive inflammation leads to various neurological and psychological complications. This review explores the pathophysiological mechanisms and associated outcomes of streptococcal meningitis, particularly its short- and long-term neurological sequelae. Neurological symptoms, such as cognitive impairment, motor deficits, and sensory loss, are shown to vary in severity, with children being particularly susceptible to lasting complications. Among survivors, hearing loss, cognitive decline, and cranial nerve palsies emerge as the most frequently reported complications. The findings highlight the need for timely intervention, including neurorehabilitation strategies that focus on optimizing recovery and mitigating long-term disabilities. Future recommendations emphasize improving early diagnosis, expanding vaccine access, and personalizing rehabilitation protocols to enhance patient outcomes. As a novel contribution, this review proposes the term “post-meningitic syndrome” to showcase the broad spectrum of CNS complications that persist following streptococcal meningitis, providing a framework for a future clinical and research focus.
... Based on these findings, we hypothesized that milk fat synthesis in A2A2 genotypes cows could be linked to g_Acetobacter and g_ Pseudomonas content. Moreover, g_Streptococcus and g_Pediococcus are lactic acid bacteria that produce lactic acid, which can be used as a substrate for secondary fermentation to produce precursors for milk fat synthesis: acetate, propionate, and butyrate (50,51). In addition to increasing energy conversion efficiency to milk fat through its involvement in amino acid biosynthesis and energy substrate metabolism, g_Streptococcus has also been positively associated with serum bile acid levels (52,53). ...
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In Holstein cows, β-casein, one of the most critical proteins in milk, exists in two main genotypes, A1 and A2. Herein, 45 Holstein cows [categorized into three groups based on β-casein A1A1, A1A2, and A2A2 genotypes (N = 15)] with the same feeding management and litter size were enrolled to explore differences in rumen microflora and metabolites across various β-casein genotypes. Rumen fluids were collected for metagenomics and metabolomics analyses. Metabolomics and weighted gene co-expression network analysis (WGCNA) revealed that arachidonic acid (AA), adrenic acid (AdA), glycocholic acid (GCA), and taurocholic acid (TCA) were significantly and positively correlated with milk fat % in dairy cows (p < 0.05). Furthermore, macro-genomics and Spearman’s correlation analysis revealed significant positive correlations (p < 0.05) between the characteristic flora (g_Acetobacter, g_Pseudoxanthomonas, g_Streptococcus, and g_Pediococcus) and the five characteristic metabolites in the rumen of A2A2 dairy cows. Moreover, functional enrichment analysis revealed more genes enriched to the TRP channel’s inflammatory mediator-regulated pathway and the mTOR signaling pathway in A2A2 genotyped cows. Additionally, the regulatory effects of AA on bovine mammary epithelial cells (BMECs) were examined using CCK-8, EdU, and qRT-PCR assays, revealing that AA promoted triglyceride (TG) synthesis and upregulated the milk fat marker genes including SREBF1, ACSS2, AGPAT6, and FASN. Overall, we identified characteristic microorganisms and metabolites in A2A2 Holstein cows and established that AA could be a biomarker for higher milk fat %.
... S. mutans enhances the cariogenic properties due to its acidogenicity, sucrose metabolism, and adherence properties [45]. In addition, L. acidophilus is also considered to be a major contributor to the increase in caries, which can act synergistically in the presence of S. mutans, creating a niche for the retention of microorganisms [46]. ...
... The most well-known microorganisms associated with dental caries are Streptococcus mutans and Lactobacilli [10][11][12]. In recent times, advancements in nanotechnology have presented opportunities for impeding the production of biofilms by surface changes and the utilization of nanoparticles [13]. ...
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This study aimed to evaluate the antimicrobial effect of coated orthodontic molar tubes (COMT) with zinc oxide nanoparticles (ZnO NPs) using an electrophoretic deposition method (EPD) and to evaluate the orthodontic molar tubes (OMT) bond failure rate. Seventy-two orthodontic molar tubes (OMTs) for second molars were divided into two groups 36 each; one group coated with ZnO NPs and the other control negative uncoated. The OMT was coated using the EPD method with ZnO NPs in a concentration of 10 g/l. The OMTs were randomly allocated using a split-mouth, cross-quadrant design. After 2 weeks of appliance placement, swabs were taken from the surface of the OMTs for microbial assessment against Streptococcus mutans, Lactobacillus acidophilus, and total bacterial counts; additionally, plaque and gingival indices were assessed. The patient was followed for 3 months to evaluate the bond failure rate. The COMT showed a statistically significant reduction in total bacterial accounts, S. mutans, and L. acidophilus compared to UOMT (P < 0.001). Furthermore, the plaque and gingival indices near COMT were significantly less than that of UOMT. The bond failure rate was not significant between the COMT and UOMT. The COMT with ZnO NPs has potent antibacterial activity against the tested pathogens with a reduction in the amount of plaque accumulation. The use of the EPD method was feasible without adverse effects on the orthodontic molar tubes bond failure rate.
... S. mutans is a acidogenic and aciduric bacteria, acting as an initiator of dental caries [40]. L. acidophilus and L. casei are major contributors to the progression of dental caries [41,42]. They produces lactic acid as the main end-product of carbohydrate fermentation, which further acidify the oral environment [43]. ...
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Objective To develop a novel calcium silver zeolite (Ca-Ag-Zeo) and assess its biocompatibility, physiochemical properties and antimicrobial effects. Methods Ca-Ag-Zeo was synthesized using ion-exchange method with calcium chloride, silver nitrate and Zeolite X (Zeo). Silver zeolite X (Ag-Zeo) and Zeo were set as control. The chemical structure, morphology, crystal structure and elemental composition of Ca-Ag-Zeo was characterized by X-ray diffraction spectrum, scanning electron microscopy, transmission electron microscopy and energy dispersive spectroscopy, respectively. Its biocompatibility on the human gingival fibroblasts was assessed by cell counting kit-8 assay. Its physiochemical properties were determined by the released calcium and silver ion using Inductive Coupled Plasma Emission Spectrometry for up to 12 weeks. The antimicrobial properties on Streptococcus mutans, Lactobacillus acidophilus, Lactobacillus casei, and Candida albicans were assessed by minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) assay. Results Ca-Ag-Zeo with a hexagonal cage structure was synthesized. As for biocompatibility, the half-maximal inhibitory concentration (± SD in mg/mL) of Ca-Ag-Zeo, Ag-Zeo and Zeo in human gingival fibroblasts were 0.52 ± 0.05, 0.15 ± 0.01 and 3.35 ± 0.58, respectively (Zeo > Ca-Ag-Zeo > Ag-Zeo; p < 0.05). As for physiochemical properties, the accumulated ion release (± SD in mg) of Ca-Ag-Zeo, Ag-Zeo and Zeo were 0.011 ± 0.003, 0 and 0 for calcium ion, respectively (Ca-Ag-Zeo > Ag-Zeo, Zeo; p < 0.001), and 0.213 ± 0.032, 0.209 ± 0.019 and 0 for silver ion, respectively (Ca-Ag-Zeo, Ag-Zeo > Zeo; p < 0.001). As for anti-microbial ability, the MBC/MFC (mg/mL) of Ca-Ag-Zeo, Ag-Zeo and Zeo were 32, 16 and > 256 against Streptococcus mutans; 32, 16, > 256 against Lactobacillus acidophilus; 16, 16, and 256 against Lactobacillus casei; 0.25, 0.125; and 2, 1, > 256 against Candida albicans, respectively. Conclusion A novel Ca-Ag-Zeo was developed. It presented better biocompatibility compared to Ag-Zeo. It released calcium and silver ions sustainably, and it could inhibit the growth of common cariogenic microorganisms.