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14 pages, 3967 KiB

Open AccessArticle

Multi-Omics Data Integration Reveals Key Variables Contributing to Subgingival Microbiome Dysbiosis-Induced Inflammatory Response in a Hyperglycemic Microenvironment

by Sarah Lafleur, Antoine Bodein, Joanna Mbuya Malaïka Mutombo, Alban Mathieu, Charles Joly Beauparlant, Xavier Minne, Fatiha Chandad, Arnaud Droit and Vanessa P. Houde

Int. J. Mol. Sci. 2023, 24(10), 8832; https://doi.org/10.3390/ijms24108832 - 16 May 2023

Cited by 1 | Viewed by 1492

Abstract

Subgingival microbiome dysbiosis promotes the development of periodontitis, an irreversible chronic inflammatory disease associated with metabolic diseases. However, studies regarding the effects of a hyperglycemic microenvironment on host–microbiome interactions and host inflammatory response during periodontitis are still scarce. Here, we investigated the impacts [...] Read more.

Subgingival microbiome dysbiosis promotes the development of periodontitis, an irreversible chronic inflammatory disease associated with metabolic diseases. However, studies regarding the effects of a hyperglycemic microenvironment on host–microbiome interactions and host inflammatory response during periodontitis are still scarce. Here, we investigated the impacts of a hyperglycemic microenvironment on the inflammatory response and transcriptome of a gingival coculture model stimulated with dysbiotic subgingival microbiomes. HGF-1 cells overlaid with U937 macrophage-like cells were stimulated with subgingival microbiomes collected from four healthy donors and four patients with periodontitis. Pro-inflammatory cytokines and matrix metalloproteinases were measured while the coculture RNA was submitted to a microarray analysis. Subgingival microbiomes were submitted to 16s rRNA gene sequencing. Data were analyzed using an advanced multi-omics bioinformatic data integration model. Our results show that the genes krt76, krt27, pnma5, mansc4, rab41, thoc6, tm6sf2, and znf506 as well as the pro-inflammatory cytokines IL-1β, GM-CSF, FGF2, IL-10, the metalloproteinases MMP3 and MMP8, and bacteria from the ASV 105, ASV 211, ASV 299, Prevotella, Campylobacter and Fretibacterium genera are key intercorrelated variables contributing to periodontitis-induced inflammatory response in a hyperglycemic microenvironment. In conclusion, our multi-omics integration analysis unveiled the complex interrelationships involved in the regulation of periodontal inflammation in response to a hyperglycemic microenvironment. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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13 pages, 291 KiB

Open AccessArticle

Correlation of Redondovirus and Entamoeba gingivalis Detections in the Human Oral Cavity Suggests That This Amoeba Is Possibly the Redondovirus Host

by Marine Makoa-Meng, Rayan Semmar, Angéline Antezack, Gwilherm Penant, Bernard La Scola, Virginie Monnet-Corti and Philippe Colson

Int. J. Mol. Sci. 2023, 24(7), 6303; https://doi.org/10.3390/ijms24076303 - 27 Mar 2023

Cited by 1 | Viewed by 1657

Abstract

The virome of the human oral cavity and the relationships between viruses and diseases such as periodontitis are scarcely deciphered. Redondoviruses were reported in the human oral cavity in 2019, including in periodontitis patients. Here, we aimed at detecting redondoviruses and at searching [...] Read more.

The virome of the human oral cavity and the relationships between viruses and diseases such as periodontitis are scarcely deciphered. Redondoviruses were reported in the human oral cavity in 2019, including in periodontitis patients. Here, we aimed at detecting redondoviruses and at searching for a potential viral host in human saliva. Non-stimulated saliva was collected between December 2020 and June 2021. These samples were tested using real-time PCR regarding the presence of redondovirus and Entamoeba gingivalis DNA. Similarity searches were performed using BLAST against eukaryotic and prokaryotic sequences from GenBank. The redondovirus DNA was detected in 46% of the 28 human saliva samples. In addition, short fragments of redondovirus genomes were detected in silico within Entamoeba sequences. Finally, Entamoeba gingivalis DNA was detected in 46% of the 28 saliva samples, with a strong correlation between redondovirus DNA and E. gingivalis DNA detections, in 93% of the cases. Regarded together, these findings and previous ones strongly support the presence of redondoviruses in the human oral cavity and their association to E. gingivalis as their likely host. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

14 pages, 5525 KiB

Open AccessArticle

On the Oral Microbiome of Oral Potentially Malignant and Malignant Disorders: Dysbiosis, Loss of Diversity, and Pathogens Enrichment

by Alejandro Herreros-Pomares, David Hervás, Leticia Bagan-Debón, Eloísa Jantus-Lewintre, Concepción Gimeno-Cardona and José Bagan

Int. J. Mol. Sci. 2023, 24(4), 3466; https://doi.org/10.3390/ijms24043466 - 09 Feb 2023

Cited by 6 | Viewed by 2179

Abstract

The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC [...] Read more.

The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL (n = 9), PVL (n = 12), OSCC (n = 10), PVL-OSCC (n = 8), and healthy (n = 11) donors were obtained. The sequence of the V3–V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and Fusobacteriota constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of Campilobacterota and lower Proteobacteria than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in Streptococcus parasanguinis, Streptococcus salivarius, Fusobacterium periodonticum, Prevotella histicola, Porphyromonas pasteri, and Megasphaera micronuciformis; PVL is enriched in Prevotella salivae, Campylobacter concisus, Dialister pneumosintes, and Schaalia odontolytica; OSCC is enriched in Capnocytophaga leadbetteri, Capnocytophaga sputigena, Capnocytophaga gingivalis, Campylobacter showae, Metamycoplasma salivarium, and Prevotella nanceiensis; and PVL-OSCC is enriched in Lachnospiraceae bacterium, Selenomonas sputigena, and Prevotella shahii. There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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13 pages, 1778 KiB

Open AccessArticle

Safety Assessment of the Modified Lactoperoxidase System—In Vitro Studies on Human Gingival Fibroblasts

by Marcin Magacz, Monika Papież, Dorota Kościelniak, Anna Jurczak, Karolina Kędziora, Elżbieta Pamuła and Wirginia Krzyściak

Int. J. Mol. Sci. 2023, 24(3), 2640; https://doi.org/10.3390/ijms24032640 - 30 Jan 2023

Cited by 1 | Viewed by 1285

Abstract

One strategy in caries prevention is to inhibit the formation of cariogenic biofilms. Attempts are being made to develop oral hygiene products enriched with various antimicrobial agents. One of them is lactoperoxidase—an enzyme that can oxidise (pseudo)halide ions to reactive products with antimicrobial [...] Read more.

One strategy in caries prevention is to inhibit the formation of cariogenic biofilms. Attempts are being made to develop oral hygiene products enriched with various antimicrobial agents. One of them is lactoperoxidase—an enzyme that can oxidise (pseudo)halide ions to reactive products with antimicrobial activity. Currently, commercially available products utilise thiocyanate as a substrate; however, several alternatives that are oxidised to products with greater antimicrobial potential have been found. In this study, toxicity against human gingival fibroblasts of the lactoperoxidase system was evaluated using four different (pseudo)halide substrate systems—thiocyanate, iodide, selenocyanate, and a mixture of thiocyanate and iodide. For this purpose, cells were treated with the systems and then apoptosis, cell cycle, intracellular glutathione concentration, and mitochondrial superoxide production were assessed. The results showed that each system, after generating 250 µM of the product, inhibited cell divisions, increased apoptosis, and increased the percentage of dead cells. It was concluded that the mechanism of the observed phenomena was not related to increased superoxide production or the depletion of glutathione concentration. These findings emphasised the need for the further in vitro and in vivo toxicity investigation of the modified lactoperoxidase system to assess its safety and the possibility of use in oral hygiene products. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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7 pages, 251 KiB

Open AccessCommunication

Salivary IgA and IgG Antibody Responses against Periodontitis-Associated Bacteria in Crohn’s Disease

by Mervi Gürsoy, Jaana Rautava, Pirkko Pussinen, Anna Karin Kristoffersen, Morten Enersen, Vuokko Loimaranta and Ulvi Kahraman Gürsoy

Int. J. Mol. Sci. 2023, 24(3), 2385; https://doi.org/10.3390/ijms24032385 - 25 Jan 2023

Cited by 4 | Viewed by 1406

Abstract

Elevated serum immunoglobulin (Ig) antibody levels are observed in Crohn’s disease patients. The aim of this study was to evaluate the salivary IgA and IgG antibody levels against Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia in Crohn’s disease [...] Read more.

Elevated serum immunoglobulin (Ig) antibody levels are observed in Crohn’s disease patients. The aim of this study was to evaluate the salivary IgA and IgG antibody levels against Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia in Crohn’s disease patients. Eighty-eight participants (47 Crohn’s disease patients and 41 systemically healthy age- and gender-matched controls) were included in the study. Oral and medical health statuses were recorded and salivary samples were collected. Salivary P. gingivalis, T. forsythia, A. actinomycetemcomitans, and P. intermedia carriage were analyzed with DNA sequencing technique, salivary levels of IgG1, IgG2, IgG3, IgG4, and IgM were measured with the Luminex^® xMAP™ technique, and salivary IgA and IgG antibody levels against P. gingivalis, T. forsythia, A. actinomycetemcomitans, and P. intermedia were detected by ELISA. As result, higher salivary IgG2 (p = 0.011) and IgG3 (p = 0.006), P. gingivalis IgA (p < 0.001), A. actinomycetemcomitans IgG (p = 0.001), and P. intermedia IgG (p < 0.001) antibody levels were detected in the Crohn’s disease group compared to the controls. Salivary P. gingivalis carriage was lower in the Crohn’s disease group in comparison to the controls (p = 0.024). In conclusion, salivary IgA antibody responses against P. gingivalis and IgG antibody responses against P. intermedia have independent associations with Crohn’s disease. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

16 pages, 4466 KiB

Open AccessArticle

Low-Diversity Microbiota in Apical Periodontitis and High Blood Pressure Are Signatures of the Severity of Apical Lesions in Humans

by Matthieu Minty, Sylvie Lê, Thibault Canceill, Charlotte Thomas, Vincent Azalbert, Pascale Loubieres, Jiuwen Sun, Jonathan Sillam, François Terce, Florence Servant, Alain Roulet, Céline Ribiere, Michel Ardouin, Jean-Philippe Mallet, Rémy Burcelin, Franck Diemer, Marie Georgelin-Gurgel and Vincent Blasco-Baque

Int. J. Mol. Sci. 2023, 24(2), 1589; https://doi.org/10.3390/ijms24021589 - 13 Jan 2023

Cited by 4 | Viewed by 1281

Abstract

(1) Background: In developed countries, the prevalence of apical periodontitis (AP) varies from 20% to 50% for reasons that could be associated with the apical periodontitis microbiota ecology. (2) Methods: We performed a clinical study in the Odontology department of Toulouse hospital in [...] Read more.

(1) Background: In developed countries, the prevalence of apical periodontitis (AP) varies from 20% to 50% for reasons that could be associated with the apical periodontitis microbiota ecology. (2) Methods: We performed a clinical study in the Odontology department of Toulouse hospital in France, to sequence the 16S rRNA gene of AP microbiota and collect clinical parameters from 94 patients. Forty-four patients were characterized with a PAI (periapical index of AP severity) score lower or equal to 3, while the others had superior scores (n = 50). (3) Results: The low diversity of granuloma microbiota is associated with the highest severity (PAI = 5) of periapical lesions (Odds Ratio 4.592, IC 95% [1.6329; 14.0728]; p = 0.001; notably, a lower relative abundance of Burkholderiaceae and a higher relative abundance of Pseudomonas and Prevotella). We also identified that high blood pressure (HBP) is associated with the increase in PAI scores. (4) Conclusions: Our data show that a low diversity of bacterial ecology of the AP is associated with severe PAI scores, suggesting a causal mechanism. Furthermore, a second risk factor was blood pressure associated with the severity of apical periodontitis. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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16 pages, 3752 KiB

Open AccessArticle

Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome

by Steven He, Rajdeep Chakraborty and Shoba Ranganathan

Int. J. Mol. Sci. 2023, 24(2), 1050; https://doi.org/10.3390/ijms24021050 - 05 Jan 2023

Cited by 4 | Viewed by 1788

Abstract

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40–50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral [...] Read more.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40–50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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Review

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15 pages, 594 KiB

Open AccessReview

Mitochondrial Dysfunction in the Pathogenesis and Treatment of Oral Inflammatory Diseases

by Zhili Dong, Liping Wu and Hong Hong

Int. J. Mol. Sci. 2023, 24(20), 15483; https://doi.org/10.3390/ijms242015483 - 23 Oct 2023

Cited by 1 | Viewed by 1995

Abstract

Oral inflammatory diseases (OIDs) include many common diseases such as periodontitis and pulpitis. The causes of OIDs consist microorganism, trauma, occlusal factors, autoimmune dis-eases and radiation therapy. When treated unproperly, such diseases not only affect oral health but also pose threat to people’s [...] Read more.

Oral inflammatory diseases (OIDs) include many common diseases such as periodontitis and pulpitis. The causes of OIDs consist microorganism, trauma, occlusal factors, autoimmune dis-eases and radiation therapy. When treated unproperly, such diseases not only affect oral health but also pose threat to people’s overall health condition. Therefore, identifying OIDs at an early stage and exploring new therapeutic strategies are important tasks for oral-related research. Mitochondria are crucial organelles for many cellular activities and disruptions of mitochondrial function not only affect cellular metabolism but also indirectly influence people’s health and life span. Mitochondrial dysfunction has been implicated in many common polygenic diseases, including cardiovascular and neurodegenerative diseases. Recently, increasing evidence suggests that mitochondrial dysfunction plays a critical role in the development and progression of OIDs and its associated systemic diseases. In this review, we elucidated the critical insights into mitochondrial dysfunction and its involvement in the inflammatory responses in OIDs. We also summarized recent research progresses on the treatment of OIDs targeting mitochondrial dysfunction and discussed the underlying mechanisms. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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20 pages, 1595 KiB

Open AccessReview

Oral–Gut Microbiota, Periodontal Diseases, and Arthritis: Literature Overview on the Role of Probiotics

by Martina Ferrillo, Amerigo Giudice, Mario Migliario, Filippo Renó, Lorenzo Lippi, Dario Calafiore, Nicola Marotta, Roberto de Sire, Leonzio Fortunato, Antonio Ammendolia, Marco Invernizzi and Alessandro de Sire

Int. J. Mol. Sci. 2023, 24(5), 4626; https://doi.org/10.3390/ijms24054626 - 27 Feb 2023

Cited by 6 | Viewed by 2514

Abstract

Periodontal diseases are oral inflammatory diseases affecting the tissues supporting and surrounding the teeth and include gingivitis and periodontitis. Oral pathogens may lead to microbial products spreading into the systemic circulation and reaching distant organs, while periodontal diseases have been related to low-grade [...] Read more.

Periodontal diseases are oral inflammatory diseases affecting the tissues supporting and surrounding the teeth and include gingivitis and periodontitis. Oral pathogens may lead to microbial products spreading into the systemic circulation and reaching distant organs, while periodontal diseases have been related to low-grade systemic inflammation. Gut and oral microbiota alterations might play a role in the pathogenesis of several autoimmune and inflammatory diseases including arthritis, considering the role of the gut–joint axis in the regulation of molecular pathways involved in the pathogenesis of these conditions. In this scenario, it is hypothesized that probiotics might contribute to the oral and intestinal micro-ecological balance and could reduce low-grade inflammation typical of periodontal diseases and arthritis. This literature overview aims to summarize state-of-the-art ideas about linkages among oral–gut microbiota, periodontal diseases, and arthritis, while investigating the role of probiotics as a potential therapeutic intervention for the management of both oral diseases and musculoskeletal disorders. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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35 pages, 1978 KiB

Open AccessReview

Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer

by Sujitha Jayaprakash, Mangala Hegde, Sosmitha Girisa, Mohammed S. Alqahtani, Mohamed Abbas, E. Hui Clarissa Lee, Kenneth Chun-Hong Yap, Gautam Sethi, Alan Prem Kumar and Ajaikumar B. Kunnumakkara

Int. J. Mol. Sci. 2022, 23(18), 10952; https://doi.org/10.3390/ijms231810952 - 19 Sep 2022

Cited by 5 | Viewed by 2644

Abstract

Esophageal cancer (EC), an aggressive and poorly understood disease, is one of the top causes of cancer-related fatalities. GLOBOCAN 2020 reports that there are 544,076 deaths and 604,100 new cases expected worldwide. Even though there are various advancements in treatment procedures, this cancer [...] Read more.

Esophageal cancer (EC), an aggressive and poorly understood disease, is one of the top causes of cancer-related fatalities. GLOBOCAN 2020 reports that there are 544,076 deaths and 604,100 new cases expected worldwide. Even though there are various advancements in treatment procedures, this cancer has been reported as one of the most difficult cancers to cure, and to increase patient survival; treatment targets still need to be established. Nuclear receptors (NRs) are a type of transcription factor, which has a key role in several biological processes such as reproduction, development, cellular differentiation, stress response, immunity, metabolism, lipids, and drugs, and are essential regulators of several diseases, including cancer. Numerous studies have demonstrated the importance of NRs in tumor immunology and proved the well-known roles of multiple NRs in modulating proliferation, differentiation, and apoptosis. There are surplus of studies conducted on NRs and their implications in EC, but only a few studies have demonstrated the diagnostic and prognostic potential of NRs. Therefore, there is still a paucity of the role of NRs and different ways to target them in EC cells to stop them from spreading malignancy. This review emphasizes the significance of NRs in EC by discussing their diverse agonists as well as antagonists and their response to tumor progression. Additionally, we emphasize NRs’ potential to serve as a novel therapeutic target and their capacity to treat and prevent EC. Full article

(This article belongs to the Special Issue Oral Microbiome and Oral Diseases)

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