Oral Microbiome and Human Systemic Health

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 13 July 2025 | Viewed by 19115

Special Issue Editors


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Guest Editor
Department of Microbiology, School of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia
Interests: oral microbiome; biofilm; antimicrobials

Special Issue Information

Dear Colleagues,

The oral microbiome is a complex ecosystem of microorganisms that inhabit the human mouth, including bacteria, viruses, fungi, and archaea. These microorganisms play a crucial role in maintaining oral health and are involved in the development of several oral diseases, such as dental caries, periodontitis, and oral cancer.

Recent research has shown that the oral microbiome also has a significant impact on human systemic health. The microorganisms in the mouth can enter the bloodstream through the oral tissues and, subsequently, impact various organ systems throughout the body.

Studies have found that an imbalanced oral microbiome can contribute to the development of several systemic diseases, including cardiovascular disease, diabetes, respiratory infections, and Alzheimer's disease. The mechanisms by which the oral microbiome impacts systemic health are complex and multifactorial, involving inflammatory processes, immune responses, and the modulation of the gut microbiome.

Understanding the complex interplay between the oral microbiome and systemic health is a rapidly growing area of research, with potential implications for disease prevention and treatment. Maintaining a healthy oral microbiome through good oral hygiene practices and a balanced diet may be an important strategy for promoting overall health and preventing chronic diseases.

Dr. Milena Radunovic
Dr. Natalia Di Pietro
Guest Editors

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Keywords

  • oral microbiome
  • systemic health
  • microorganisms
  • chronic diseases
  • immune responses

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Published Papers (10 papers)

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Research

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9 pages, 3789 KiB  
Article
Optimizing Red Light-Based Photodynamic Therapy for Effective Bactericidal Action Against Fusobacterium nucleatum Subspecies
by Jianglan Li, Takayuki Nambu, Chao Wang, Hiroki Takigawa, Hugo Maruyama, Chiho Mashimo and Toshinori Okinaga
Pathogens 2024, 13(11), 1016; https://doi.org/10.3390/pathogens13111016 - 19 Nov 2024
Viewed by 660
Abstract
Fusobacterium nucleatum (F. nucleatum), a key pathogen implicated in periodontal disease, contributes to oral biofilm maturation and is linked to development of systemic diseases like colorectal cancer and liver cirrhosis. Photodynamic therapy (PDT) combined with 5-aminolevulinic acid (5-ALA) treatment (ALA-PDT) selectively [...] Read more.
Fusobacterium nucleatum (F. nucleatum), a key pathogen implicated in periodontal disease, contributes to oral biofilm maturation and is linked to development of systemic diseases like colorectal cancer and liver cirrhosis. Photodynamic therapy (PDT) combined with 5-aminolevulinic acid (5-ALA) treatment (ALA-PDT) selectively targets F. nucleatum by inducing porphyrin accumulation. The bactericidal effect of red light-based PDT on F. nucleatum has not been evaluated previously. This study investigates the effect of ALA-PDT using red light-emitting diode (LED) light on F. nucleatum subspecies and their porphyrin accumulation. F. nucleatum subspecies were cultured with varying concentrations of 5-ALA under anaerobic conditions. Porphyrin accumulation was measured via fluorescence spectroscopy, and colony-forming units were measured to determine bacterial viability post-treatment. Additionally, other subspecies responded well to 0.01% 5-ALA, and uroporphyrin I accumulation correlated with bacterial death, revealing optimal bactericidal conditions. These results suggest that optimizing light intensity and 5-ALA concentration can significantly enhance the therapeutic potential of ALA-PDT in oral healthcare. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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13 pages, 847 KiB  
Article
Oral Prevalence of Selenomonas noxia Differs among Orthodontic Patients Compared to Non-Orthodontic Controls: A Retrospective Biorepository Analysis
by Kyle Hodges, Payton Famuliner, Karl Kingsley and Katherine M. Howard
Pathogens 2024, 13(8), 670; https://doi.org/10.3390/pathogens13080670 - 8 Aug 2024
Viewed by 797
Abstract
The oral microbial flora may be significantly altered by orthodontic therapy and the use of fixed orthodontic brackets. Most orthodontic research has focused on cariogenic pathogens, while some evidence has demonstrated an increase in many known periodontal pathogens. However, little is known about [...] Read more.
The oral microbial flora may be significantly altered by orthodontic therapy and the use of fixed orthodontic brackets. Most orthodontic research has focused on cariogenic pathogens, while some evidence has demonstrated an increase in many known periodontal pathogens. However, little is known about the prevalence of the Gram-negative periodontal pathogen Selenomonas noxia (SN) among these patients. Using an existing saliva biorepository, n = 208 samples from adult and pediatric orthodontic and non-orthodontic patients were identified and screened for the presence of SN using qPCR and validated primers. In the pediatric study sample (n = 89), 36% tested positive for the presence of SN, with orthodontic patients comprising more SN-positive samples (87.5%) than SN-negative samples (78.9%), p = 0.0271. In the adult study sample (n = 119), SN was found in 28.6%, with orthodontic patients comprising 58.8% of positive samples and only 28.2% of negative samples (p < 0.0001). These data demonstrated that both pediatric and adult orthodontic patients exhibited higher prevalence of SN compared with age-matched non-orthodontic controls. As this microorganism is associated not only with periodontal disease but also long-term health issues such as obesity, more research is needed regarding the factors that increase the prevalence of this microbe. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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12 pages, 255 KiB  
Article
Prevalence of Subgingival Aggregatibacter actinomycetemcomitans: Descriptive Cross-Sectional Study
by Nabil Khzam, Omar Kujan, Dorte Haubek, Aysen Arslan, Anders Johansson, Jan Oscarsson, Zeinab Razooqi and Leticia Algarves Miranda
Pathogens 2024, 13(7), 531; https://doi.org/10.3390/pathogens13070531 - 24 Jun 2024
Cited by 3 | Viewed by 1370
Abstract
This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. [...] Read more.
This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. The identification of A. actinomycetemcomitans was performed using quantitative polymerase chain reaction. A descriptive analysis, a chi-square test, and a binary logistic regression statistical evaluation were performed. The prevalence of A. actinomycetemcomitans in this population of 156 participants was 17.30% (27 patients). The prevalence of stage-III periodontitis was 75.6% and greater in older men, while the prevalence of stage-IV periodontitis was 22.4% and greater in younger women. We observed a significant relation between the risk of severe periodontitis (stage-IV) and poor oral hygiene (p = 0.006), attendance at dental appointments (p ≤ 0.001), and familial history of periodontitis (p = 0.032). In conclusion, twenty-seven individuals were positive for A. actinomycetemcomitans. Poor oral hygiene, family history of periodontitis, and irregular attendance at dental appointments were identified as potential risk factors for severe periodontitis in this cohort. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
11 pages, 382 KiB  
Article
Higher Prevalence of the Periodontal Pathogen Selenomonas noxia among Pediatric and Adult Patients May Be Associated with Overweight and Obesity
by Austin Williams, Jace Porter, Karl Kingsley and Katherine M. Howard
Pathogens 2024, 13(4), 338; https://doi.org/10.3390/pathogens13040338 - 19 Apr 2024
Cited by 2 | Viewed by 1587
Abstract
New evidence has suggested that oral and gut microflora may have significant impacts on the predisposition, development, and stability of obesity in adults over time—although less is known about this phenomenon in children. Compared with healthy-weight controls, overweight and obese adult patients are [...] Read more.
New evidence has suggested that oral and gut microflora may have significant impacts on the predisposition, development, and stability of obesity in adults over time—although less is known about this phenomenon in children. Compared with healthy-weight controls, overweight and obese adult patients are now known to harbor specific pathogens, such as Selenomonas noxia (S. noxia), that are capable of digesting normally non-digestible cellulose and fibers that significantly increase caloric extraction from normal dietary intake. To evaluate this phenomenon, clinical saliva samples (N = 122) from subjects with a normal BMI (18–25) and a BMI over 25 (overweight, obese) from an existing biorepository were screened using qPCR. The prevalence of S. noxia in samples from normal-BMI participants were lower (21.4%) than in overweight-BMI (25–29; 46.1%) and obese-BMI (30 and above; 36.8%) samples—a strong, positive correlation that was not significantly affected by age or race and ethnicity. These data strongly suggest that S. noxia may be intricately associated with overweight and obesity among patients, and more research will be needed to determine the positive and negative feedback mechanisms that may be responsible for these observations as well as the interventions needed to remove or reduce the potential effects of this oral pathogen. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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18 pages, 5441 KiB  
Article
Oral Microbiome Stamp in Alzheimer’s Disease
by Argul Issilbayeva, Aiym Kaiyrlykyzy, Elizaveta Vinogradova, Zharkyn Jarmukhanov, Samat Kozhakhmetov, Aliya Kassenova, Madiyar Nurgaziyev, Nurislam Mukhanbetzhanov, Dinara Alzhanova, Gulnaz Zholdasbekova, Sholpan Askarova and Almagul R. Kushugulova
Pathogens 2024, 13(3), 195; https://doi.org/10.3390/pathogens13030195 - 23 Feb 2024
Cited by 5 | Viewed by 2639
Abstract
Recent studies have suggested that periodontal disease and alterations in the oral microbiome may be associated with cognitive decline and Alzheimer’s disease (AD) development. Here, we report a case-control study of oral microbiota diversity in AD patients compared to healthy seniors from Central [...] Read more.
Recent studies have suggested that periodontal disease and alterations in the oral microbiome may be associated with cognitive decline and Alzheimer’s disease (AD) development. Here, we report a case-control study of oral microbiota diversity in AD patients compared to healthy seniors from Central Asia. We have characterized the bacterial taxonomic composition of the oral microbiome from AD patients (n = 64) compared to the healthy group (n = 71) using 16S ribosomal RNA sequencing. According to our results, the oral microbiome of AD has a higher microbial diversity, with an increase in Firmicutes and a decrease in Bacteroidetes in the AD group. LEfSe analysis showed specific differences at the genus level in both study groups. A region-based analysis of the oral microbiome compartment in AD was also performed, and specific differences were identified, along with the absence of differences in bacterial richness and on the functional side. Noteworthy findings demonstrated the decrease in periodontitis-associated bacteria in the AD group. Distinct differences were revealed in the distribution of metabolic pathways between the two study groups. Our study confirms that the oral microbiome is altered in AD. However, a comprehensive picture of the complete composition of the oral microbiome in patients with AD requires further investigation. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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12 pages, 2385 KiB  
Article
Streptococcus mitis and Prevotella melaninogenica Influence Gene Expression Changes in Oral Mucosal Lesions in Periodontitis Patients
by Uros Tomic, Nadja Nikolic, Jelena Carkic, Djordje Mihailovic, Drago Jelovac, Jelena Milasin and Ana Pucar
Pathogens 2023, 12(10), 1194; https://doi.org/10.3390/pathogens12101194 - 26 Sep 2023
Cited by 1 | Viewed by 2185
Abstract
Oral microbiome disruptions in periodontitis are related to the chronic inflammatory reactions that could in turn lead to the development of multiple oral diseases. The objective of the study was to assess the frequencies of Streptococcus mitis, Prevotella melaninogenica, and Prevotella [...] Read more.
Oral microbiome disruptions in periodontitis are related to the chronic inflammatory reactions that could in turn lead to the development of multiple oral diseases. The objective of the study was to assess the frequencies of Streptococcus mitis, Prevotella melaninogenica, and Prevotella intermedia in oral benign lesions, oral potentially malignant disorders (OPMDs), and oral squamous cell carcinomas (OSCCs) and investigate the impact of these bacteria on the expression patterns of the selected (potential) target genes (PI3CA/AKT2/mTOR, DUSP16/MAPK14, and COX2). After sample collection (25 benign lesions, 30 OPMDs, and 35 OSCCs) and DNA/RNA extraction, quantitative real-time polymerase chain reaction (qPCR) was performed to detect bacterial presence and assess relative gene expression levels in different lesion groups. Prevotella melaninogenica was the most prevalent of the three analyzed bacteria, with the frequency being 60% in benign lesions, 87% in OPMDs (p = 0.024), and 77% in OSCC. The OPMD tissues in which Prevotella melaninogenica was present exhibited a higher expression level of AKT2 (p = 0.042). Significantly lower expression of DUSP16 was observed in OSCC tissues containing Streptococcus mitis (p = 0.011). The obtained results indicate a substantial contribution of P. melaninogenica and Str. mitis in the pathogenesis of oral mucosal lesions, possibly via AKT2 upregulation and DUSP16 downregulation. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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Review

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15 pages, 1893 KiB  
Review
Global Research Trends in the Links between Periodontal Disease and Cancer: A Bibliometric Analysis
by Suh-Woan Hu, Jaw-Ji Yang and Yuh-Yih Lin
Pathogens 2024, 13(9), 789; https://doi.org/10.3390/pathogens13090789 - 12 Sep 2024
Viewed by 1181
Abstract
Both periodontal disease and cancer are prevalent conditions with significant impacts on individuals and society. Extensive research has suggested a potential link between these two diseases. This study conducted a bibliometric analysis using the Thomson Reuters Web of Science Core Collection database, focusing [...] Read more.
Both periodontal disease and cancer are prevalent conditions with significant impacts on individuals and society. Extensive research has suggested a potential link between these two diseases. This study conducted a bibliometric analysis using the Thomson Reuters Web of Science Core Collection database, focusing on publications from 2014 to 2023. The analysis included data extraction and examination of authors, affiliations, publication dates, journals, countries, citation counts, keywords, and the H-index. A total of 253 relevant articles were identified, showing an increasing trend in both publications and citations over the years. The analysis highlighted the most productive authors, institutions, and countries/regions, with Michaud DS and Abnet CC leading in the number of publications. Highly cited articles emphasized the role of specific oral microbiota, particularly F. nucleatum and P. gingivalis, in various cancers, suggesting their potential as diagnostic markers and therapeutic targets. Four key thematic clusters emerged from the keyword analysis: the broader health implications of periodontal disease, the microbiome’s role in carcinogenesis, inflammation, and specific bacteria in cancer, and epidemiological methods in studying the disease–cancer association. This bibliometric analysis underscores the growing interest in the connection between periodontal disease and cancer. Future research should adopt interdisciplinary approaches, focus on large-scale microbiome studies and longitudinal research to understand the systemic effects of periodontal disease, identify cancer-associated bacterial profiles, and investigate the molecular mechanisms of bacterial carcinogenesis. Additionally, public health interventions aimed at improving oral hygiene and reducing cancer risk factors are recommended. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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18 pages, 1233 KiB  
Review
The Bacterial Oral Microbiome in Children with Congenital Heart Disease: An Extensive Review
by Maria Hofmann, Nelly Schulz-Weidner, Norbert Krämer and Torsten Hain
Pathogens 2023, 12(10), 1269; https://doi.org/10.3390/pathogens12101269 - 21 Oct 2023
Cited by 2 | Viewed by 1978
Abstract
Children with congenital heart disease have poorer oral health compared with healthy children. Oral diseases, such as dental caries and gingivitis, are associated with the oral microbiome. The objective of this review was to find evidence of differences in the bacterial colonization of [...] Read more.
Children with congenital heart disease have poorer oral health compared with healthy children. Oral diseases, such as dental caries and gingivitis, are associated with the oral microbiome. The objective of this review was to find evidence of differences in the bacterial colonization of the oral cavity of children with congenital heart disease (CHD) versus healthy children. A literature review was conducted according to predetermined criteria, including the need for controlled clinical trials. Half of the 14 studies that met the inclusion criteria reported significant differences in bacterial colonization in children with congenital heart disease. A variety of influencing factors were discussed. There is some evidence for alterations in the oral microflora as a result of physiopathological and treatment-related factors in children with CHD, but additional research is required to validate these findings. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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23 pages, 4768 KiB  
Review
Evaluating Alterations of the Oral Microbiome and Its Link to Oral Cancer among Betel Quid Chewers: Prospecting Reversal through Probiotic Intervention
by Prerna Diwan, Mohit Nirwan, Mayank Bahuguna, Shashi Prabha Kumari, James Wahlang and Rakesh Kumar Gupta
Pathogens 2023, 12(8), 996; https://doi.org/10.3390/pathogens12080996 - 30 Jul 2023
Cited by 3 | Viewed by 2668
Abstract
Areca nut and slaked lime, with or without tobacco wrapped in Piper betle leaf, prepared as betel quid, is extensively consumed as a masticatory product in many countries across the world. Betel Quid can promote the malignant transformation of oral lesions as well [...] Read more.
Areca nut and slaked lime, with or without tobacco wrapped in Piper betle leaf, prepared as betel quid, is extensively consumed as a masticatory product in many countries across the world. Betel Quid can promote the malignant transformation of oral lesions as well as trigger benign cellular and molecular changes. In the oral cavity, it causes changes at the compositional level in oral microbiota called dysbiosis. This dysbiosis may play an important role in Oral Cancer in betel quid chewers. The abnormal presence and increase of bacteria Fusobacterium nucleatum, Capnocytophaga gingivalis, Prevotella melaninogenica, Peptostreptococcus sp., Porphyromonas gingivalis, and Streptococcus mitis in saliva and/or other oral sites of the cancer patients has attracted frequent attention for its association with oral cancer development. In the present review, the authors have analysed the literature reports to revisit the oncogenic potential of betel quid and oral microbiome alterations, evaluating the potential of oral microbiota both as a driver and biomarker of oral cancer. The authors have also shared a perspective that the restoration of local microbiota can become a potentially therapeutic or prophylactic strategy for the delay or reversal of lip and oral cavity cancers, especially in high-risk population groups. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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Other

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19 pages, 3407 KiB  
Systematic Review
Difference in the Intestinal Microbiota between Breastfeed Infants and Infants Fed with Artificial Milk: A Systematic Review
by Francesco Inchingolo, Angelo Michele Inchingolo, Giulia Latini, Laura Ferrante, Elisabetta de Ruvo, Merigrazia Campanelli, Marialuisa Longo, Andrea Palermo, Alessio Danilo Inchingolo and Gianna Dipalma
Pathogens 2024, 13(7), 533; https://doi.org/10.3390/pathogens13070533 - 24 Jun 2024
Cited by 4 | Viewed by 2488
Abstract
The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed [...] Read more.
The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed infants with that of F-fed infants and to evaluate the clinical implications of these differences. We searched databases on Scopus, Web of Science, and Pubmed with the following keywords: “gut microbiota”, “gut microbiome”, and “neonatal milk”. The inclusion criteria were articles relating to the analysis of the intestinal microbiome of newborns in relation to the type of nutrition, clinical studies or case series, excluding reviews, meta-analyses, animal models, and in vitro studies. The screening phase ended with the selection of 13 publications for this work. Breastfed infants showed higher levels of beneficial bacteria such as Bifidobacterium and Lactobacillus, while F-fed infants had a higher prevalence of potentially pathogenic bacteria, including Clostridium difficile and Enterobacteriaceae. Infant feeding type influences the composition of oral GM significantly. Breastfeeding promotes a healthier and more diverse microbial ecosystem, which may offer protective health benefits. Future research should explore strategies to improve the GM of F-fed infants and understand the long-term health implications. Full article
(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)
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