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Molecular Advances in Oral Microbiome and Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 August 2024) | Viewed by 11223

Special Issue Editors


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Guest Editor
Kornberg School of Dentistry, Temple University, Philadelphia, PA 19140, USA
Interests: molecular microbial ecology; microbiome; oral diseases; bioinformatics; next generation sequencing; microbiology

Special Issue Information

Dear Colleagues,

The oral microbiome is the second largest and most diverse microbiome in human body after the gut microbiome. In the state of equilibrium, the oral microbiome maintains a state of homeostasis and health in the oral cavity. However, an imbalance or dysbiosis of the oral microbiome can manifest into a range of oral diseases. Recent advances in oral and microbial research have shown that the role of oral microbes is not limited to the oral cavity. Instead, they are also closely associated with overall health and other diseases like diabetes, metabolic syndrome, cancers specifically oral and orodigestive cancers. Understanding the complex interactions between oral microbes, each other and the host will have future implications in the diagnosis and prevention of various health conditions.   

The goal of this Special Issue is to advance our understanding of oral microbial communities, their function and composition, and their roles in the states of health and diseases. We welcome studies of oral microbiome that highlight the emerging evidences of various roles of oral microbiome in maintaining health and in diseases. Authors are invited to submit original research articles and reviews to this Special Issue. Submissions may include (but are not limited to) the following themes:

  • Molecular mechanisms of oral microbes and host defenses;
  • Microbial interferences in dental treatments;
  • Oral bacteria and general health;
  • Oral microbes as potential biomarkers;
  • Role of microbes in oral cancer;
  • Understaing of ecology and functions of oral biofilms.

Dr. Divyashri Baraniya
Prof. Dr. Babak Baban
Guest Editors

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Keywords

  • oral microbiome
  • oral cavity
  • biofilm
  • host–microbe interaction
  • dysbiosis

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Published Papers (7 papers)

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Research

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19 pages, 2919 KiB  
Article
Experimental Inoculation of Aggregatibacter actinomycetemcomitans and Streptococcus gordonii and Its Impact on Alveolar Bone Loss and Oral and Gut Microbiomes
by Catarina Medeiros Rocha, Dione Kawamoto, Fernando Henrique Martins, Manuela Rocha Bueno, Karin H. Ishikawa, Ellen Sayuri Ando-Suguimoto, Aline Ramos Carlucci, Leticia Sandoli Arroteia, Renato V. Casarin, Luciana Saraiva, Maria Regina Lorenzetti Simionato and Marcia Pinto Alves Mayer
Int. J. Mol. Sci. 2024, 25(15), 8090; https://doi.org/10.3390/ijms25158090 - 25 Jul 2024
Viewed by 749
Abstract
Oral bacteria are implicated not only in oral diseases but also in gut dysbiosis and inflammatory conditions throughout the body. The periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) often occurs in complex oral biofilms with Streptococcus gordonii (Sg), and this interaction [...] Read more.
Oral bacteria are implicated not only in oral diseases but also in gut dysbiosis and inflammatory conditions throughout the body. The periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) often occurs in complex oral biofilms with Streptococcus gordonii (Sg), and this interaction might influence the pathogenic potential of this pathogen. This study aims to assess the impact of oral inoculation with Aa, Sg, and their association (Aa+Sg) on alveolar bone loss, oral microbiome, and their potential effects on intestinal health in a murine model. Sg and/or Aa were orally administered to C57Bl/6 mice, three times per week, for 4 weeks. Aa was also injected into the gingiva three times during the initial experimental week. After 30 days, alveolar bone loss, expression of genes related to inflammation and mucosal permeability in the intestine, serum LPS levels, and the composition of oral and intestinal microbiomes were determined. Alveolar bone resorption was detected in Aa, Sg, and Aa+Sg groups, although Aa bone levels did not differ from that of the SHAM-inoculated group. Il-1β expression was upregulated in the Aa group relative to the other infected groups, while Il-6 expression was downregulated in infected groups. Aa or Sg downregulated the expression of tight junction genes Cldn 1, Cldn 2, Ocdn, and Zo-1 whereas infection with Aa+Sg led to their upregulation, except for Cldn 1. Aa was detected in the oral biofilm of the Aa+Sg group but not in the gut. Infections altered oral and gut microbiomes. The oral biofilm of the Aa group showed increased abundance of Gammaproteobacteria, Enterobacterales, and Alloprevotella, while Sg administration enhanced the abundance of Alloprevotella and Rothia. The gut microbiome of infected groups showed reduced abundance of Erysipelotrichaceae. Infection with Aa or Sg disrupts both oral and gut microbiomes, impacting oral and gut homeostasis. While the combination of Aa with Sg promotes Aa survival in the oral cavity, it mitigates the adverse effects of Aa in the gut, suggesting a beneficial role of Sg associations in gut health. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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14 pages, 1990 KiB  
Article
Increased IL-12p70 and IL-8 Produced by Monocytes in Response to Streptococcus spp. and Actinomyces spp. Causals of Endodontic Primary Infections
by Raquel Sánchez-Gutiérrez, Janeth Araujo-Pérez, Diana Lorena Alvarado-Hernández, Ana María González-Amaro, Verónica Méndez-González, Bruno Rivas-Santiago, Roberto González-Amaro, Amaury Pozos-Guillén and Marlen Vitales-Noyola
Int. J. Mol. Sci. 2023, 24(23), 16853; https://doi.org/10.3390/ijms242316853 - 28 Nov 2023
Cited by 1 | Viewed by 1261
Abstract
We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14+, CD4+, CD8+, CD19+ and Tregs Foxp3+. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral [...] Read more.
We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14+, CD4+, CD8+, CD19+ and Tregs Foxp3+. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral blood samples, which were taken from patients with primary infections. Cellular cultures were performed with peripheral blood mononuclear cells (PBMC) with and without Actinomyces spp. and Streptococcus spp. during 48, 72, and 96 h of contact in culture (concentration 5 × 105 cells/well) in a round plate bound with 48 wells. Later, PBMC was collected for analysis by flow cytometry, with the monoclonal antibodies αCD14, αCD4, αCD8, αCD19 and αFoxp3, and acquired using an FACSCanto II cytometer. The supernatant of cellular cultures was analyzed for the quantification of inflammatory cytokines. Data analysis was performed in FlowJo v10.8.2 and FCAPArray software, and statistical analysis was performed using GraphPad v5.0. software. We observed an increase in the percentage of CD14+ cells in patients at different hours of cellular culture in the presence of both Actinomyces spp. and Streptococcus spp. microorganisms, compared to healthy controls. This study demonstrates the role played by the innate immune system in the pathogeny of endodontic primary infections, explaining the effects that generate the more common microorganisms in this oral pathology. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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22 pages, 4374 KiB  
Article
Amyloid Fibrils Produced by Streptococcus sanguinis Contribute to Biofilm Formation and Immune Evasion
by Eduardo M. Franco, Lívia A. Alves, Hassan Naveed, Victor A. A. Freitas, Débora C. Bastos and Renata O. Mattos-Graner
Int. J. Mol. Sci. 2023, 24(21), 15686; https://doi.org/10.3390/ijms242115686 - 28 Oct 2023
Cited by 2 | Viewed by 1638
Abstract
Bacterial surface proteins assembled into amyloids contribute to biofilm formation and host immune evasion. Streptococcus sanguinis, a pioneer colonizer of teeth commonly involved in cardiovascular infections, expresses about thirty-three proteins anchored to the cell wall by sortase A. Here, we characterized the [...] Read more.
Bacterial surface proteins assembled into amyloids contribute to biofilm formation and host immune evasion. Streptococcus sanguinis, a pioneer colonizer of teeth commonly involved in cardiovascular infections, expresses about thirty-three proteins anchored to the cell wall by sortase A. Here, we characterized the production of amyloid in S. sanguinis strains differing in biofilm and immune evasion phenotypes and investigated the role of sortase A in amyloidogenesis. Amyloid was identified in biofilms formed by nine strains, using Congo red (CR) staining and cross-polarized light microscopy. Additionally, EGCG, an amyloid inhibitor, impaired biofilm maturation in a strain-specific fashion. The amounts of amyloid-like components quantified in culture fluids of nine strains using thioflavin T and fluorimetry negatively correlated with bacterial binding to complement-activating proteins (SAP, C1q), C3b deposition and rates of opsonophagocytosis in PMNs, implying amyloid production in immune evasion. The deletion of the sortase A gene (srtA) in strain SK36 compromised amyloid production and sucrose-independent biofilm maturation. The srtA mutant further showed increased susceptibility to C3b deposition and altered interactions with PMNs as well as reduced persistence in human blood. These findings highlight the contribution of amyloids to biofilm formation and host immune evasion in S. sanguinis strains, further indicating the participation of sortase A substrates in amyloidogenesis. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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17 pages, 2227 KiB  
Article
Obesity Is Associated with the Severity of Periodontal Inflammation Due to a Specific Signature of Subgingival Microbiota
by Sylvie Lê, Sara Laurencin-Dalicieux, Matthieu Minty, Justine Assoulant-Anduze, Alexia Vinel, Noor Yanat, Pascale Loubieres, Vincent Azalbert, Swann Diemer, Remy Burcelin, Thibault Canceill, Charlotte Thomas and Vincent Blasco-Baque
Int. J. Mol. Sci. 2023, 24(20), 15123; https://doi.org/10.3390/ijms242015123 - 12 Oct 2023
Cited by 4 | Viewed by 1492
Abstract
The aim of this study was to analyze the link between periodontal microbiota and obesity in humans. We conducted a cohort study including 45 subjects with periodontitis divided into two groups: normo-weighted subjects with a body mass index (BMI) between 20 and 25 [...] Read more.
The aim of this study was to analyze the link between periodontal microbiota and obesity in humans. We conducted a cohort study including 45 subjects with periodontitis divided into two groups: normo-weighted subjects with a body mass index (BMI) between 20 and 25 kg/m2 (n = 34) and obese subjects with a BMI > 30 kg/m2 (n = 11). Our results showed that obesity was associated with significantly more severe gingival inflammation according to Periodontal Inflamed Surface Area (PISA index). Periodontal microbiota taxonomic analysis showed that the obese (OB) subjects with periodontitis were characterized by a specific signature of subgingival microbiota with an increase in Gram-positive bacteria in periodontal pockets, associated with a decrease in microbiota diversity compared to that of normo-weighted subjects with periodontitis. Finally, periodontal treatment response was less effective in OB subjects with persisting periodontal inflammation, reflecting a still unstable periodontal condition and a risk of recurrence. To our knowledge, this study is the first exploring both salivary and subgingival microbiota of OB subjects. Considering that OB subjects are at higher periodontal risk, this could lead to more personalized preventive or therapeutic strategies for obese patients regarding periodontitis through the specific management of oral microbiota of obese patients. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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14 pages, 2040 KiB  
Article
Porphyromonas gingivalis Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis
by Zsombor Prucsi, Agnieszka Zimny, Alicja Płonczyńska, Natalia Zubrzycka, Jan Potempa and Maja Sochalska
Int. J. Mol. Sci. 2023, 24(16), 12922; https://doi.org/10.3390/ijms241612922 - 18 Aug 2023
Cited by 4 | Viewed by 1751
Abstract
Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis, Porphyromonas gingivalis has been identified as a keystone pathogen. The immune-modulatory function of P. gingivalis is well characterized, but the [...] Read more.
Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis, Porphyromonas gingivalis has been identified as a keystone pathogen. The immune-modulatory function of P. gingivalis is well characterized, but the mechanism by which this bacterium secretes peptidyl arginine deiminase (PPAD), a protein/peptide citrullinating enzyme, thus contributing to the infinite feed-forward loop of inflammation, is not fully understood. To determine the functional role of citrullination in periodontitis, neutrophils were stimulated by P. gingivalis bearing wild-type PPAD and by a PPAD mutant strain lacking an active enzyme. Flow cytometry showed that PPAD contributed to prolonged neutrophil survival upon bacterial stimulation, accompanied by the secretion of aberrant IL-6 and TNF-α. To further assess the complex mechanism by which citrullination sustains a chronic inflammatory state, the ROS production and phagocytic activity of neutrophils were evaluated. Flow cytometry and colony formation assays showed that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines, while enhancing the resilience of the bacteria to phagocytosis. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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Review

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14 pages, 1279 KiB  
Review
Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options
by Sapir Jelin-Uhlig, Markus Weigel, Benjamin Ott, Can Imirzalioglu, Hans-Peter Howaldt, Sebastian Böttger and Torsten Hain
Int. J. Mol. Sci. 2024, 25(15), 8053; https://doi.org/10.3390/ijms25158053 - 24 Jul 2024
Viewed by 1066
Abstract
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote [...] Read more.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms “microbiome”, “osteonecrosis of the jaws”, and “bisphosphonates”. Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces, Fusobacterium, and Streptococcus. It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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26 pages, 603 KiB  
Review
Systemic Antibiotic Use in Acute Irreversible Pulpitis: Evaluating Clinical Practices and Molecular Insights
by Shahnawaz Khijmatgar, Gionata Bellucci, Luca Creminelli, Giulia Margherita Tartaglia, Jr. and Margherita Tumedei
Int. J. Mol. Sci. 2024, 25(2), 1357; https://doi.org/10.3390/ijms25021357 - 22 Jan 2024
Cited by 1 | Viewed by 2527
Abstract
This scoping review systematically evaluates the use of systemic antibiotics in treating acute irreversible pulpitis, integrating clinical practice patterns with recent molecular insights. We analyzed clinical evidence on antibiotic prescription trends among dental professionals and examined molecular research advancements in relation to pulpitis. [...] Read more.
This scoping review systematically evaluates the use of systemic antibiotics in treating acute irreversible pulpitis, integrating clinical practice patterns with recent molecular insights. We analyzed clinical evidence on antibiotic prescription trends among dental professionals and examined molecular research advancements in relation to pulpitis. This review is intended to bridge the gap between clinical practice and molecular research, guiding more evidence-based approaches to treating acute irreversible pulpitis. Electronic databases were searched for relevant articles published in English based on the objective of the review. A second search using all identified keywords and index terms was undertaken across all the included databases. In addition, a reference list of identified articles was searched. Studies including original research, systematic reviews, meta-analyses, clinical trials, and observational and retrospective studies, all written in English and published from 2010 onwards, were included, and an analysis of the text words contained in the titles and abstracts of the retrieved papers and of the index terms used to describe the articles was performed. A total of N = 53 articles were selected. Altogether, N = 43 (76.79%) articles were cross-sectional studies, N = 4 (11.11%) were systematic reviews, and N = 3 (5.36%) were guidelines. The most frequent level of evidence was level VI (N = 43 (76.79%). The mean percentage of dentists who prescribed antibiotics to treat acute irreversible pulpitis was 23.89 ± 23.74% (range: 0.05–75.7). Similarly, for specialists, it was 22.41 ± 15.64 (range 2.2–50.4), and the percentage for undergraduates was 17.52 ± 20.59 (range 0–62.6). The significant developments in research models for pulpitis research and the characterisation of biomarkers have led to better management strategies. Concurrently, significant advancements in molecular research provide new understandings of pulpitis, suggesting alternative therapeutic approaches. Although there are guidelines available, increased rates of antibiotic prescription are still prevalent around the globe. Full article
(This article belongs to the Special Issue Molecular Advances in Oral Microbiome and Diseases)
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