The Oral Microbiome in Systemic Health and Disease: Therapeutics for Reversing Microbial Dysbiosis and Applications in Precision Medicine

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 48439

Special Issue Editors


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Guest Editor
Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
Interests: oral health; oral disease; salivary microbiome; microbial diversity; cariogenic microorganisms

E-Mail Website
Guest Editor
Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
Interests: oral health; oral disease; microbiota

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Guest Editor
Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
Interests: bone resorption; microbiota and disease

Special Issue Information

Dear Colleagues,

The oral microbiome is a complex collection of microbial species, the balance of which contributes to the initiation and development of oral infectious disease processes, including dental caries, periodontitis and endodontic pathoses.  Current evidence also indicates that the oral microbiome can influence or is associated with systemic health and disease, including the development of cardiovascular disease, atherosclerosis, diabetes, and rheumatoid arthritis.  Although the oral microbiome exhibits natural defenses to drastic shifts in microbial composition via the effects of saliva and other factors, it also has the capacity to recover from disease states induced by the overabundance of specific oral pathogens. Following administration of antibiotics or probiotics, the oral microbiota exhibits resilience and eventual recovery from microbial dysbiosis, whereas the gut microbiota tends to sustain long-term modifications.  In research from our laboratory, we have identified microorganisms that are associated with caries-active children and have determined that povidone iodine is an effective adjunctive therapy that has the potential to shift the composition of the cariogenic microbiome to one more closely aligned with non-cariogenic health.

The objectives of this special Issue, The Oral Microbiome in Systemic Health and Disease: Therapeutics for Reversing Microbial Dysbiosis and Applications in Precision Medicine, are to define the role of the oral microbiome in systemic health and disease, as well as to describe the therapies that can potentially reverse or rebalance the oral microbiome towards health.

As Guest Editor and Co-Editors of this special issue, we invite you to contribute manuscripts and to help define the current state of science on therapies and precision medicine approaches leading to the restoration of the oral microbiome towards sustained oral and systemic health.

Prof. Dr. Curtis A. Machida
Assistant Professor Tom J. Maier
Prof. Nasser Said-Al-Naief
Guest Editors

Manuscript Submission Information

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Keywords

  • oral microbiome
  • oral infectious disease
  • systemic health and disease
  • therapeutics
  • microbial dysbiosis
  • microbial rebalancing
  • precision medicine

Published Papers (10 papers)

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Editorial

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4 pages, 173 KiB  
Editorial
Oral Microbiome in Health and Disease: Maintaining a Healthy, Balanced Ecosystem and Reversing Dysbiosis
by Tom Maier
Microorganisms 2023, 11(6), 1453; https://doi.org/10.3390/microorganisms11061453 - 31 May 2023
Viewed by 2685
Abstract
The oral microbiome is a complex and dynamic assemblage of microorganisms that normally exist within the mouth, contributing to host health via a number of mechanisms, including exclusion of harmful microbes and immune optimization [...] Full article

Research

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12 pages, 1703 KiB  
Article
Oral Factors That Impact the Oral Microbiota in Parkinson’s Disease
by Natalia S. Rozas, Gena D. Tribble and Cameron B. Jeter
Microorganisms 2021, 9(8), 1616; https://doi.org/10.3390/microorganisms9081616 - 29 Jul 2021
Cited by 19 | Viewed by 3175
Abstract
Patients with Parkinson’s disease (PD) are at increased risk of aspiration pneumonia, their primary cause of death. Their oral microbiota differs from healthy controls, exacerbating this risk. Our goal was to explore if poor oral health, poor oral hygiene, and dysphagia status affect [...] Read more.
Patients with Parkinson’s disease (PD) are at increased risk of aspiration pneumonia, their primary cause of death. Their oral microbiota differs from healthy controls, exacerbating this risk. Our goal was to explore if poor oral health, poor oral hygiene, and dysphagia status affect the oral microbiota composition of these patients. In this cross-sectional case-control study, the oral microbiota from hard and soft tissues of patients with PD (n = 30) and age-, gender-, and education-matched healthy controls (n = 30) was compared using 16S rRNA gene sequencing for bacterial identification. Study participants completed dietary, oral hygiene, drooling, and dysphagia questionnaires, and an oral health screening. Significant differences in soft tissue beta-diversity (p < 0.005) were found, and a higher abundance of opportunistic oral pathogens was detected in patients with PD. Factors that significantly influenced soft tissue beta-diversity and microbiota composition include dysphagia, drooling (both p < 0.05), and salivary pH (p < 0.005). Thus, patients with PD show significant differences in their oral microbiota compared to the controls, which may be due, in part, to dysphagia, drooling, and salivary pH. Understanding factors that alter their oral microbiota could lead to the development of diagnostic and treatment strategies that improve the quality of life and survivability of these patients. Full article
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13 pages, 3388 KiB  
Article
Salivary Microbiome Diversity in Kuwaiti Adolescents with Varied Body Mass Index—A Pilot Study
by Hend Alqaderi, Meganathan P. Ramakodi, Rasheeba Nizam, Sindhu Jacob, Sriraman Devarajan, Muthukrishnan Eaaswarkhanth and Fahd Al-Mulla
Microorganisms 2021, 9(6), 1222; https://doi.org/10.3390/microorganisms9061222 - 04 Jun 2021
Cited by 5 | Viewed by 3158
Abstract
The potential role of the salivary microbiome in human diseases has increasingly been explored. The salivary microbiome has been characterized in several global populations, except the Arabian Gulf region. Hence, in this pilot study, we profiled the salivary microbiome of Kuwaiti adolescents with [...] Read more.
The potential role of the salivary microbiome in human diseases has increasingly been explored. The salivary microbiome has been characterized in several global populations, except the Arabian Gulf region. Hence, in this pilot study, we profiled the salivary microbiome of Kuwaiti adolescents with varied body mass indexes (BMI). The analyses of core microbiome composition showed Firmicutes, Bacteroidota, Proteobacteria, Patescibacteria, Fusobacteriota, Actinobacteriota, and Campylobacterota as the common phylum found in the Kuwaiti adolescent population. We also illustrated a diverse microbial community among the sampled individuals grouped according to their BMI. Notably, the overweight group was found with a higher number of distinct taxa than other groups. As such, the core microbiome composition was found to be significantly different (p-value < 0.001) across different BMI groups. Overall, this pilot investigation outlined the microbial diversity and suggested that changes in salivary microbiome composition in people with obese or overweight BMI might reflect their susceptibility to oral diseases. Full article
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15 pages, 278 KiB  
Article
Microbiologic Profiles of Patients with Dental Prosthetic Treatment and Periodontitis before and after Photoactivation Therapy—Randomized Clinical Trial
by Raluca Cristina Mocanu, Maria-Alexandra Martu, Ionut Luchian, Irina Georgeta Sufaru, George Alexandru Maftei, Nicoleta Ioanid, Silvia Martu and Monica Tatarciuc
Microorganisms 2021, 9(4), 713; https://doi.org/10.3390/microorganisms9040713 - 30 Mar 2021
Cited by 24 | Viewed by 2003
Abstract
Fixed prosthodontic dental restorations can potentially affect the periodontal tissues and vice versa, the periodontium can influence the longevity and esthetic appearance of dental restorations. We proposed an investigation on total bacterial load, specific periodontal pathogens, and periodontal clinical parameters in patients with [...] Read more.
Fixed prosthodontic dental restorations can potentially affect the periodontal tissues and vice versa, the periodontium can influence the longevity and esthetic appearance of dental restorations. We proposed an investigation on total bacterial load, specific periodontal pathogens, and periodontal clinical parameters in patients with dental fixed prosthesis and different degrees of periodontal tissue loss that followed photoactivation therapy (PDT) adjunctive to scaling and root planing. The study was conducted on 160 subjects, which were randomly assigned to scaling and root planing (SRP) alone (52 subjects, 256 sites), SRP and chlorhexidine rinsing (58 subjects, 276 sites), and SRP plus PDT (50 subjects, 318 sites). Periodontal parameters (plaque index, bleeding on probing, probing depth, and clinical attachment loss), followed by total bacterial load and specific periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) were examined in each patient at baseline, one and six months after. PDT exerted significant improvements both in clinical and microbiological load after one month, and these results were maintained 6 months after when compared to chlorhexidine rinsing or SRP alone, especially in severe periodontitis cases. Photoactivation therapy as an adjunctive periodontal therapeutic method was efficient in offering supplementary periodontal improvements in the clinical and microbiological parameters of patients with fixed dental prosthesis, particularly in severe periodontitis cases. Full article
9 pages, 2413 KiB  
Communication
Deep Ultraviolet Light-Emitting Diode Light Therapy for Fusobacterium nucleatum
by Soichiro Fukuda, Shunsuke Ito, Jun Nishikawa, Tatsuya Takagi, Naoto Kubota, Ken-ichiro Otsuyama, Hidehiro Tsuneoka, Junzo Nojima, Koji Harada, Katsuaki Mishima, Yutaka Suehiro, Takahiro Yamasaki and Isao Sakaida
Microorganisms 2021, 9(2), 430; https://doi.org/10.3390/microorganisms9020430 - 19 Feb 2021
Cited by 3 | Viewed by 2745
Abstract
Background: Fusobacterium nucleatum, which is associated with periodontitis and gingivitis, has been detected in colorectal cancer (CRC). Methods: We evaluated the bactericidal effect of deep ultraviolet (DUV) light-emitting diode (LED) light therapy on F. nucleatum both qualitatively and quantitatively. Two DUV-LEDs with [...] Read more.
Background: Fusobacterium nucleatum, which is associated with periodontitis and gingivitis, has been detected in colorectal cancer (CRC). Methods: We evaluated the bactericidal effect of deep ultraviolet (DUV) light-emitting diode (LED) light therapy on F. nucleatum both qualitatively and quantitatively. Two DUV-LEDs with peak wavelengths of 265 and 280-nm were used. DNA damage to F. nucleatum was evaluated by the production of cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts (6–4PP). Results: DUV-LEDs showed a bactericidal effect on F. nucleatum. No colony growth was observed after 3 min of either 265 nm or 280 nm DUV-LED irradiation. The survival rates of F. nucleatum under 265 nm DUV-LED light irradiation dropped to 0.0014% for 10 s and to 0% for 20 s irradiation. Similarly, the survival rate of F. nucleatum under 280 nm DUV-LED light irradiation dropped to 0.00044% for 10 s and 0% for 20 s irradiation. The irradiance at the distance of 35 mm from the DUV-LED was 0.265 mW/cm2 for the 265 nm LED and 0.415 mW/cm2 for the 280 nm LED. Thus, the radiant energy for lethality was 5.3 mJ/cm2 for the 265 nm LED and 8.3 mJ/cm2 for the 280 nm LED. Amounts of CPD and 6–4PP in F. nucleatum irradiated with 265 nm DUV-LED light were 6.548 ng/µg and 1.333 ng/µg, respectively. Conclusions: DUV-LED light exerted a bactericidal effect on F. nucleatum by causing the formation of pyrimidine dimers indicative of DNA damage. Thus, DUV-LED light therapy may have the potential to prevent CRC. Full article
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Review

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23 pages, 884 KiB  
Review
The Role of the Oral Microbiota in the Etiopathogenesis of Oral Squamous Cell Carcinoma
by Tereza Vyhnalova, Zdenek Danek, Daniela Gachova and Petra Borilova Linhartova
Microorganisms 2021, 9(8), 1549; https://doi.org/10.3390/microorganisms9081549 - 21 Jul 2021
Cited by 31 | Viewed by 4962
Abstract
Dysbiosis in the oral environment may play a role in the etiopathogenesis of oral squamous cell carcinoma (OSCC). This review aims to summarize the current knowledge about the association of oral microbiota with OSCC and to describe possible etiopathogenetic mechanisms involved in processes [...] Read more.
Dysbiosis in the oral environment may play a role in the etiopathogenesis of oral squamous cell carcinoma (OSCC). This review aims to summarize the current knowledge about the association of oral microbiota with OSCC and to describe possible etiopathogenetic mechanisms involved in processes of OSCC development and progression. Association studies included in this review were designed as case–control/case studies, analyzing the bacteriome, mycobiome, and virome from saliva, oral rinses, oral mucosal swabs, or oral mucosal tissue samples (deep and superficial) and comparing the results in healthy individuals to those with OSCC and/or with premalignant lesions. Changes in relative abundances of specific bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.) and fungi (especially Candida sp.) were associated with OSCC. Viruses can also play a role; while the results of studies investigating the role of human papillomavirus in OSCC development are controversial, Epstein–Barr virus was positively correlated with OSCC. The oral microbiota has been linked to tumorigenesis through a variety of mechanisms, including the stimulation of cell proliferation, tumor invasiveness, angiogenesis, inhibition of cell apoptosis, induction of chronic inflammation, or production of oncometabolites. We also advocate for the necessity of performing a complex analysis of the microbiome in further studies and of standardizing the sampling procedures by establishing guidelines to support future meta-analyses. Full article
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20 pages, 1403 KiB  
Review
Pre and Probiotics Involved in the Modulation of Oral Bacterial Species: New Therapeutic Leads in Mental Disorders?
by Yoann Maitre, Rachid Mahalli, Pierre Micheneau, Alexis Delpierre, Marie Guerin, Gilles Amador and Frédéric Denis
Microorganisms 2021, 9(7), 1450; https://doi.org/10.3390/microorganisms9071450 - 06 Jul 2021
Cited by 12 | Viewed by 4143
Abstract
This systematic review aims to identify probiotics and prebiotics for modulating oral bacterial species associated with mental disorders. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline, we search the electronic MEDLINE database published till January 2021 to identify the studies [...] Read more.
This systematic review aims to identify probiotics and prebiotics for modulating oral bacterial species associated with mental disorders. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline, we search the electronic MEDLINE database published till January 2021 to identify the studies on probiotics and/or prebiotics for preventing and treating major oral dysbiosis that provokes mental disorders. The outcome of the search produces 374 records. After excluding non-relevant studies, 38 papers were included in the present review. While many studies suggest the potential effects of the oral microbiota on the biochemical signalling events between the oral microbiota and central nervous system, our review highlights the limited development concerning the use of prebiotics and/or probiotics in modulating oral dysbiosis potentially involved in the development of mental disorders. However, the collected studies confirm prebiotics and/or probiotics interest for a global or targeted modulation of the oral microbiome in preventing or treating mental disorders. These outcomes also offer exciting prospects for improving the oral health of people with mental disorders in the future. Full article
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18 pages, 1541 KiB  
Review
Infective Endocarditis: A Focus on Oral Microbiota
by Carmela Del Giudice, Emanuele Vaia, Daniela Liccardo, Federica Marzano, Alessandra Valletta, Gianrico Spagnuolo, Nicola Ferrara, Carlo Rengo, Alessandro Cannavo and Giuseppe Rengo
Microorganisms 2021, 9(6), 1218; https://doi.org/10.3390/microorganisms9061218 - 04 Jun 2021
Cited by 39 | Viewed by 10337
Abstract
Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced [...] Read more.
Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced diagnosis remain the most important strategies to fight this disease. In this regard, it is worth noting that for over 50 years, oral microbiota has been considered one of the significant risk factors for IE. Indeed, among the disparate recommendations from the American heart association and the European Society of Cardiology, there are good oral hygiene and prophylaxis for high-risk patients undergoing dental procedures. Thus, significant interest has grown in the role of oral microbiota and it continues to be a subject of research interest, especially if we consider that antimicrobial treatments can generate drug-resistant mutant bacteria, becoming a severe social problem. This review will describe the current knowledge about the relationship between oral microbiota, dental procedures, and IE. Further, it will discuss current methods used to prevent IE cases that originate from oral pathogens and how these should be focused on improving oral hygiene, which remains the significant persuasible way to prevent bacteremia and systemic disorders. Full article
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16 pages, 1197 KiB  
Review
Oral Microbiota and Salivary Levels of Oral Pathogens in Gastro-Intestinal Diseases: Current Knowledge and Exploratory Study
by Maria Contaldo, Alessandra Fusco, Paola Stiuso, Stefania Lama, Antonietta Gerarda Gravina, Annalisa Itro, Alessandro Federico, Angelo Itro, Gianna Dipalma, Francesco Inchingolo, Rosario Serpico and Giovanna Donnarumma
Microorganisms 2021, 9(5), 1064; https://doi.org/10.3390/microorganisms9051064 - 14 May 2021
Cited by 35 | Viewed by 3473
Abstract
Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. This paper aims to review the current knowledge and report the preliminary data on salivary [...] Read more.
Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. This paper aims to review the current knowledge and report the preliminary data on salivary levels of Fusobacterium nucleatum, Porphyromonas gingivalis and Candida albicans in subjects with different gastro-intestinal conditions or pathologies, in order to determine any differences. The null hypothesis was “subjects with different gastro-intestinal diseases do not show significant differences in the composition of the oral microbiota”. Twenty-one subjects undergoing esophagastroduodenoscopy or colonscopy were recruited. For each subject, a salivary sample was collected before the endoscopy procedure, immediately stored at −20 °C and subsequently used for genomic bacterial DNA extraction by real-time PCR. Low levels of F. nucleatum and P. gingivalis were peculiar in the oral microbiota in subjects affected by Helicobater pylori-negative chronic gastritis without cancerization and future studies will elucidate this association. The level of C. albicans did not statistically differ among groups. This preliminary study could be used in the future, following further investigation, as a non-invasive method for the search of gastrointestinal diseases and associated markers. Full article
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22 pages, 2216 KiB  
Review
Interconnections between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance between Systemic Health and Disease
by Brandon Khor, Michael Snow, Elisa Herrman, Nicholas Ray, Kunal Mansukhani, Karan A. Patel, Nasser Said-Al-Naief, Tom Maier and Curtis A. Machida
Microorganisms 2021, 9(3), 496; https://doi.org/10.3390/microorganisms9030496 - 26 Feb 2021
Cited by 36 | Viewed by 10373
Abstract
The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of [...] Read more.
The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration. Full article
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