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The Oral Microbiome in Health and Disease

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dentistry, Oral Surgery and Oral Medicine".

Deadline for manuscript submissions: closed (15 January 2021) | Viewed by 52589

Special Issue Editors


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Department of Fundamental and Clinical Biological Sciences, Systemic Healthcare Laboratory EA 4129, University of Lyon, 69007 Lyon, France
Interests: microbiology; infectiology; molecular biology; nanoparticles; cosmetics
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Special Issue Information

Dear Colleagues,

The area of oral microbiome research in health and diseases is on the move. New knowledge suggests that the oral microbiome is a key factor in the protection against the colonization of extrinsic pathogens that could impact systemic health. However, the imbalance of the ecosystem, which can be caused by a weak immune system, leads to a challenge for oral and systemic health. The ecological conditions of these habitats are constantly changing, so ecosystems are subject to frequent variations.

Several researchers and practitioners have discussed the clinical impact of individual behavior on the oral health component. Maintaining a clinical symbiotic environment for oral microbiota contributes to the symbiosis of human microbiomes. The recent “keystone pathogen hypothesis” considers that certain bacteria in low quantities can act on the host immune system and convert the microbiota from symbiotic to dysbiotic to provoke inflammatory disease. There are also some hypotheses that periodontal pathogens contribute to the increased the risk of non-communicable diseases marginalizing the impact of conventional risk factors such as tobacco use and alcohol.

In general, there is an agreement that the reestablishment of symbiotic interdental microbiota and the disappearance of interdental inflammation could contribute to reestablishing the symbiosis of the salivary and oral microbiota. In the medium term, this could significantly reduce the incidence and/or severity of periodontal diseases. In the long term, the oral microbiome should contribute to reducing risk, morbidity, and mortality, mainly related to systemic diseases such as cardiovascular diseases, diabetes, cancers, and chronic respiratory diseases.

The present Special Issue aims to deepen the specificity of the biological and clinical mechanisms associated with the oral microbiome in health and disease. Although the association is not fully established and the biological mechanisms are not yet fully understood, there is an obligation of precautionary principles and preventive measures to reduce any potential risk factors. In summary, the theoretical approach of considering and preventing certain daily behaviors of patients for a potential gain in oral health from a reduction in a virulent bacterial load could have direct or indirect positive effects on general health and even prevent the possibility of such an association. This is an opportunity to seriously attend to the care of the patients who suffer from a lack of control over their behaviors and to increase the knowledge of clinicians in a field that is still little explored.

Prof. Dr. Denis Bourgeois
Dr. Florence Carrouel
Guest Editors

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Keywords

  • chronic diseases
  • individual prophylaxis
  • nutrition
  • oral microbiome
  • periodontal diseases
  • predictors
  • risk factors

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

8 pages, 254 KiB  
Editorial
COVID-19: A Recommendation to Examine the Effect of Mouthrinses with β-Cyclodextrin Combined with Citrox in Preventing Infection and Progression
by Florence Carrouel, Maria Pia Conte, Julian Fisher, Lucio Souza Gonçalves, Claude Dussart, Juan Carlos Llodra and Denis Bourgeois
J. Clin. Med. 2020, 9(4), 1126; https://doi.org/10.3390/jcm9041126 - 15 Apr 2020
Cited by 102 | Viewed by 13441
Abstract
Considered to be a major portal of entry for infectious agents, the oral cavity is directly associated with the evolutionary process of SARS-CoV-2 in its inhalation of ambient particles in the air and in expectorations. Some new generations of mouth rinses currently on [...] Read more.
Considered to be a major portal of entry for infectious agents, the oral cavity is directly associated with the evolutionary process of SARS-CoV-2 in its inhalation of ambient particles in the air and in expectorations. Some new generations of mouth rinses currently on the market have ingredients that could contribute to lower the SARS-CoV-2 viral load, and thus facilitate the fight against oral transmission. If chlorhexidine, a usual component of mouth rinse, is not efficient to kill SARS-CoV-2, the use of a mouth rinses and/or with local nasal applications that contain β-cyclodextrins combined with flavonoids agents, such as Citrox, could provide valuable adjunctive treatment to reduce the viral load of saliva and nasopharyngeal microbiota, including potential SARS-CoV-2 carriage. We urge national agencies and authorities to start clinical trials to evaluate the preventive effects of βCD-Citrox therapeutic oral biofilm rinses in reducing the viral load of the infection and possibly disease progression. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)

Research

Jump to: Editorial, Review

14 pages, 8286 KiB  
Article
Evaluation of Microcirculation, Cytokine Profile, and Local Antioxidant Protection Indices in Periodontal Health, and Stage II, Stage III Periodontitis
by Artem Eldzharov, Dzerassa Kabaloeva, Dmitry Nemeryuk, Aida Goncharenko, Adelina Gatsalova, Elena Ivanova, Igor Kostritskiy, Florence Carrouel and Denis Bourgeois
J. Clin. Med. 2021, 10(6), 1262; https://doi.org/10.3390/jcm10061262 - 18 Mar 2021
Cited by 11 | Viewed by 2520
Abstract
Periodontitis, initiated by the subgingival biofilm and modified by the individual’s inflammatory/immune response, has been associated with vascular dysfunction. To analyze microcirculation indices in periodontal tissues and determine the activity of the enzymatic component of antioxidant defense and humoral immunity factors, a single-blind [...] Read more.
Periodontitis, initiated by the subgingival biofilm and modified by the individual’s inflammatory/immune response, has been associated with vascular dysfunction. To analyze microcirculation indices in periodontal tissues and determine the activity of the enzymatic component of antioxidant defense and humoral immunity factors, a single-blind non-invasive clinical trial was realized. Forty subjects, aged from 30 to 65 years, with moderate to severe chronic periodontitis (chronic generalized periodontitis, CGP) vs. 40 subjects as periodontally healthy were recruited. Information such as capillary diameter, capillary blood flow velocity, concentration of pro- and anti-inflammatory cytokines in serum, vascular endothelial growth factor, and enzymatic component of antioxidant protection were taken. The revealed microcirculatory dysfunctions in patients with CGP clearly demonstrate the progressive disorder of periodontal tissue perfusion and oxygenation, the presence of increased vascular permeability and functional failure of the microvascular system in the lesion. Cytokine profile of CGP patients’ blood serum demonstrated a significant increase of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), IL-4 levels as well as statistically significant decrease of IL-1ra, IL-10 concentration. Participants with CGP demonstrated a dominant superiority of IgM and IgG levels. In conclusion, these results contribute to a better understanding of potential correlation between microvascular changes and local and systemic markers of inflammation. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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26 pages, 889 KiB  
Article
Nutrition as a Key Modifiable Factor for Periodontitis and Main Chronic Diseases
by Prescilla Martinon, Laurie Fraticelli, Agnes Giboreau, Claude Dussart, Denis Bourgeois and Florence Carrouel
J. Clin. Med. 2021, 10(2), 197; https://doi.org/10.3390/jcm10020197 - 7 Jan 2021
Cited by 90 | Viewed by 10448
Abstract
Nutrition is recognized as an essential component in the prevention of a number of chronic diseases, including periodontal disease. Based on these considerations, a better understanding is required regarding how the diet, and more particularly the intake of macronutrients and micronutrients, could impact [...] Read more.
Nutrition is recognized as an essential component in the prevention of a number of chronic diseases, including periodontal disease. Based on these considerations, a better understanding is required regarding how the diet, and more particularly the intake of macronutrients and micronutrients, could impact the potential relationship between nutrition and periodontal diseases, periodontal diseases and chronic diseases, nutrition and chronic diseases. To overcome this complexity, an up-to-date literature review on the nutriments related to periodontal and chronic diseases was performed. High-sugar, high-saturated fat, low-polyols, low-fiber and low-polyunsaturated-fat intake causes an increased risk of periodontal diseases. This pattern of nutrients is classically found in the Western diet, which is considered as an ‘unhealthy’ diet that causes cardiovascular diseases, diabetes and cancers. Conversely, low-sugar, high-fiber and high-omega-6-to-omega-3 fatty acid ratio intake reduces the risk of periodontal diseases. The Mediterranean, DASH, vegetarian and Okinawa diets that correspond to these nutritional intakes are considered as ‘healthy’ diets, reducing this risk of cardiovascular diseases, diabetes and cancers. The role of micronutrients, such as vitamin D, E, K and magnesium, remains unclear, while others, such as vitamin A, B, C, calcium, zinc and polyphenols have been shown to prevent PDs. Some evidence suggests that probiotics and prebiotics could promote periodontal health. Periodontal and chronic diseases share, with a time delay, nutrition as a risk factor. Thus, any change in periodontal health should be considered as a warning signal to control the dietary quality of patients and thus reduce the risk of developing chronic diseases later on. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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19 pages, 6496 KiB  
Article
Oral Microbiome Signatures in Hematological Cancers Reveal Predominance of Actinomyces and Rothia Species
by Jean-Luc C. Mougeot, Micaela F. Beckman, Holden C. Langdon, Michael T. Brennan and Farah Bahrani Mougeot
J. Clin. Med. 2020, 9(12), 4068; https://doi.org/10.3390/jcm9124068 - 17 Dec 2020
Cited by 14 | Viewed by 3386
Abstract
The endogenous microbiome of healthy individuals in oral cavities is diverse, representing over 700 bacterial species. Imbalance in oral and gut microbiome composition and associated gene expression has been linked to different forms of hematological (blood) cancers. Our objective is to compare oral [...] Read more.
The endogenous microbiome of healthy individuals in oral cavities is diverse, representing over 700 bacterial species. Imbalance in oral and gut microbiome composition and associated gene expression has been linked to different forms of hematological (blood) cancers. Our objective is to compare oral microbiome profiles of patients with blood cancers (BC group: N = 39 patients, n = 124 oral samples) to those of healthy control subjects (HC group: N = 27 subjects, n = 100 oral samples). Saliva samples and swabs of buccal mucosa, supragingival plaque, and tongue were collected from blood cancer patients and healthy controls. Next-generation sequencing (16S-rRNA gene V3–V4 region) was used to determine the relative abundance of bacterial taxa present at the genus and species levels. Differences in oral microbiome beta-diversity were determined using multivariate permutational analysis of variance (PERMANOVA). Linear discriminant analysis (LDA) effect size (LEfSe) analysis was performed to identify differentiating bacterial taxa in pairwise comparisons. The PATRICv3.6.7 online tool was used to determine the predominance of potential pathogenicity in the BC group. The oral microbiome beta-diversities of the BC and HC groups differed and corresponded to a reduced alpha-diversity in the BC group. LEfSe analysis showed significant LDA scores for Actinomyces and Rothia spp., differentiating the BC group from the HC group. In silico analysis using PATRICv3.6.7 demonstrated that the groups of bacteria possessing traits of “antibiotic resistance”, “oral pathogen”, and “virulence” was enriched in the BC group. Although 56% of the BC patients received antibiotics within two weeks of the oral bacterial sampling, Actinomyces genus remained the top differentiating feature in the BC group regardless of the administration of antibiotics, while Rothia dentocariosa was detected as the top differentiating feature in the BC patients who did not receive antibiotics, but not in those who received antibiotics. Further investigation is needed to better understand the interactions of certain oral species with the host immune system to better characterize clinically relevant associations with hematological cancers. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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12 pages, 2005 KiB  
Article
Changes in the Salivary Metabolic Profile of Generalized Periodontitis Patients after Non-surgical Periodontal Therapy: A Metabolomic Analysis Using Nuclear Magnetic Resonance Spectroscopy
by Filippo Citterio, Federica Romano, Gaia Meoni, Giovanni Iaderosa, Silvia Grossi, Alberto Sobrero, Francesca Dego, Matteo Corana, Giovanni Nicolao Berta, Leonardo Tenori and Mario Aimetti
J. Clin. Med. 2020, 9(12), 3977; https://doi.org/10.3390/jcm9123977 - 8 Dec 2020
Cited by 16 | Viewed by 2623
Abstract
Pattern analysis of the salivary metabolic profile has been proven accurate in discriminating between generalized periodontitis (GP) patients and healthy individuals (HI), as this disease modifies the salivary concentrations of specific metabolites. Due to the scarcity of data from previous studies, this study [...] Read more.
Pattern analysis of the salivary metabolic profile has been proven accurate in discriminating between generalized periodontitis (GP) patients and healthy individuals (HI), as this disease modifies the salivary concentrations of specific metabolites. Due to the scarcity of data from previous studies, this study aimed to evaluate if non-surgical periodontal therapy (NST) could affect the metabolomic profile in GP patients’ saliva and if it compares to that of HI. Unstimulated salivary samples were collected from 11 HI and 12 GP patients before and 3 months after NST. Nuclear Magnetic Resonance (NMR) spectroscopy, followed by a supervised multivariate statistical approach on entire saliva spectra and partial least square (PLS) discriminant analysis, were performed to obtain metabolic profiles. In the GP group, periodontal treatment improved all clinical parameters, but not all the diseased sites were eradicated. PLS revealed an accuracy of 100% in distinguishing between metabolic profiles of GP patients before and after NST. Orthogonal projection to latent structure was able to discriminate between the three groups of subjects with an accuracy of 85.6%. However, the post-NST metabolic profile of GP patients could not be completely assimilated to that of HI. Although NST may produce significant changes in the metabolic profile, GP patients maintained a distinctive fingerprint compared to HI. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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12 pages, 1001 KiB  
Article
Expression of Inflammatory Markers RANK, MMP-9 and PTHrP in Chronic Apical Periodontitis from People Living with HIV Undergoing Antiretroviral Therapy
by Marcio Francisco Pereira, Fabio Ramoa Pires, Luciana Armada, Dennis Carvalho Ferreira, Florence Carrouel, Denis Bourgeois and Lucio Souza Gonçalves
J. Clin. Med. 2020, 9(11), 3611; https://doi.org/10.3390/jcm9113611 - 9 Nov 2020
Cited by 5 | Viewed by 2066
Abstract
To compare the expression of the receptor activator of nuclear factor-kappa B (RANK), matrix metalloproteinase 9 (MMP-9) and parathyroid hormone-related protein (PTHrP) in primary chronic apical periodontitis lesions (CAPLs) between people living with HIV (PLWHIV) undergoing antiretroviral therapy (ART) and HIV- individuals, 32 [...] Read more.
To compare the expression of the receptor activator of nuclear factor-kappa B (RANK), matrix metalloproteinase 9 (MMP-9) and parathyroid hormone-related protein (PTHrP) in primary chronic apical periodontitis lesions (CAPLs) between people living with HIV (PLWHIV) undergoing antiretroviral therapy (ART) and HIV- individuals, 32 CAPLs (16 lesions from each group) were submitted to histopathological and immunohistochemical analyses and compared between groups. The majority of the PLWHIV group had undetectable plasma viral loads (n = 13; 81.3%). The means of TCD4+ lymphocytes, exposure to HIV-1 and the time of the use of ART were 542.1 cells/mm3 (SD = 256.4), 6.3 years (SD = 2.9) and 5.0 years (SD = 2.5), respectively. Of all variables studied, only histopathological diagnosis showed a significant difference between groups (LWHIV: granuloma n = 11 (68.0%); cyst n = 5 (31.2%); HIV-: granuloma n = 15 (93.8%); cyst n = 1 (6.2%); p = 0.015). When comparing the expressions of the three inflammatory markers between the groups, no significant differences were seen. There was no difference in the expression of RANK, PTHrP and MMP-9 in primary chronic apical periodontitis lesions between PLWHIV under ART and HIV- individuals. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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17 pages, 3088 KiB  
Article
Microbial Analysis of Saliva to Identify Oral Diseases Using a Point-of-Care Compatible qPCR Assay
by Pune N. Paqué, Christopher Herz, Joël S. Jenzer, Daniel B. Wiedemeier, Thomas Attin, Nagihan Bostanci, Georgios N. Belibasakis, Kai Bao, Philipp Körner, Tanja Fritz, Julia Prinz, Patrick R. Schmidlin, Thomas Thurnheer, Florian J. Wegehaupt, Konstantinos Mitsakakis and Johannes R. Peham
J. Clin. Med. 2020, 9(9), 2945; https://doi.org/10.3390/jcm9092945 - 11 Sep 2020
Cited by 19 | Viewed by 4436
Abstract
Oral health is maintained by a healthy microbiome, which can be monitored by state-of-the art diagnostics. Therefore, this study evaluated the presence and quantity of ten oral disease-associated taxa (P. gingivalis, T. forsythia, T. denticola, F. nucleatum, C. rectus [...] Read more.
Oral health is maintained by a healthy microbiome, which can be monitored by state-of-the art diagnostics. Therefore, this study evaluated the presence and quantity of ten oral disease-associated taxa (P. gingivalis, T. forsythia, T. denticola, F. nucleatum, C. rectus, P. intermedia, A. actinomycetemcomitans, S. mutans, S. sobrinus, oral associated Lactobacilli) in saliva and their clinical status association in 214 individuals. Upon clinical examination, study subjects were grouped into healthy, caries and periodontitis and their saliva was collected. A highly specific point-of-care compatible dual color qPCR assay was developed and used to study the above-mentioned bacteria of interest in the collected saliva. Assay performance was compared to a commercially available microbial reference test. Eight out of ten taxa that were investigated during this study were strong discriminators between the periodontitis and healthy groups: C. rectus, T. forsythia, P. gingivalis, S. mutans, F. nucleatum, T. denticola, P. intermedia and oral Lactobacilli (p < 0.05). Significant differentiation between the periodontitis and caries group microbiome was only shown for S. mutans (p < 0.05). A clear distinction between oral health and disease was enabled by the analysis of quantitative qPCR data of target taxa levels in saliva. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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Review

Jump to: Editorial, Research

27 pages, 1914 KiB  
Review
Resolving the Contradictory Functions of Lysine Decarboxylase and Butyrate in Periodontal and Intestinal Diseases
by Martin Levine and Zsolt M. Lohinai
J. Clin. Med. 2021, 10(11), 2360; https://doi.org/10.3390/jcm10112360 - 27 May 2021
Cited by 6 | Viewed by 3514
Abstract
Periodontal disease is a common, bacterially mediated health problem worldwide. Mastication (chewing) repeatedly traumatizes the gingiva and periodontium, causing traces of inflammatory exudate, gingival crevicular fluid (GCF), to appear in crevices between the teeth and gingiva. Inadequate tooth cleaning causes a dentally adherent [...] Read more.
Periodontal disease is a common, bacterially mediated health problem worldwide. Mastication (chewing) repeatedly traumatizes the gingiva and periodontium, causing traces of inflammatory exudate, gingival crevicular fluid (GCF), to appear in crevices between the teeth and gingiva. Inadequate tooth cleaning causes a dentally adherent microbial biofilm composed of commensal salivary bacteria to appear around these crevices where many bacteria grow better on GCF than in saliva. We reported that lysine decarboxylase (Ldc) from Eikenella corrodens depletes the GCF of lysine by converting it to cadaverine and carbon dioxide. Lysine is an amino acid essential for the integrity and continuous renewal of dentally attached epithelium acting as a barrier to microbial products. Unless removed regularly by oral hygiene, bacterial products invade the lysine-deprived dental attachment where they stimulate inflammation that enhances GCF exudation. Cadaverine increases and supports the development of a butyrate-producing microbiome that utilizes the increased GCF substrates to slowly destroy the periodontium (dysbiosis). A long-standing paradox is that acid-induced Ldc and butyrate production support a commensal (probiotic) microbiome in the intestine. Here, we describe how the different physiologies of the respective tissues explain how the different Ldc and butyrate functions impact the progression and control of these two chronic diseases. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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15 pages, 361 KiB  
Review
Could Periodontal Disease through Periopathogen Fusobacterium nucleatum Be an Aggravating Factor for Gastric Cancer?
by Petra Șurlin, Flavia Mirela Nicolae, Valeriu Marin Șurlin, Ștefan Pătrașcu, Bogdan Silviu Ungureanu, Andreea Cristiana Didilescu and Dan Ionuț Gheonea
J. Clin. Med. 2020, 9(12), 3885; https://doi.org/10.3390/jcm9123885 - 29 Nov 2020
Cited by 14 | Viewed by 3517
Abstract
Periodontal disease affects the supporting tissues of the teeth, being a chronic inflammatory disease caused by specific microorganisms from subgingival biofilm. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that acts as a periodontal pathogen, being an important factor in linking Gram-positive and Gram-negative [...] Read more.
Periodontal disease affects the supporting tissues of the teeth, being a chronic inflammatory disease caused by specific microorganisms from subgingival biofilm. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that acts as a periodontal pathogen, being an important factor in linking Gram-positive and Gram-negative bacteria in the periodontal biofilm, but its involvement in systemic diseases has also been found. Several studies regarding the implication of Fusobacterium nucleatum in gastro-enterological cancers have been conducted. The present review aims to update and systematize the latest information about Fusobacterium nucleatum in order to evaluate the possibility of an association between periodontal disease and the evolution of gastroenterological cancers through the action of Fusobacterium nucleatum, highlighting gastric cancer. This would motivate future research on the negative influence of periodontal pathology on the evolution of gastric cancer in patients suffering from both pathologies. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
20 pages, 391 KiB  
Review
Did the Brain and Oral Microbiota Talk to Each Other? A Review of the Literature
by Yoann Maitre, Pierre Micheneau, Alexis Delpierre, Rachid Mahalli, Marie Guerin, Gilles Amador and Frederic Denis
J. Clin. Med. 2020, 9(12), 3876; https://doi.org/10.3390/jcm9123876 - 28 Nov 2020
Cited by 37 | Viewed by 5369
Abstract
This systematic review aims to investigate the role of the oral microbiome in the pathophysiology of mental health disorders and to appraise the methodological quality of research of the oral–brain axis which is a growing interest area. The PRISMA guideline was adopted, to [...] Read more.
This systematic review aims to investigate the role of the oral microbiome in the pathophysiology of mental health disorders and to appraise the methodological quality of research of the oral–brain axis which is a growing interest area. The PRISMA guideline was adopted, to carry out an electronic search through the MEDLINE database, to identify studies that have explored the role of the oral microbiome in the pathophysiology of mental health disorders published from 2000 up to June 2020. The search resulted in 140 records; after exclusions, a total of 22 papers were included in the present review. In accordance with the role of the oral microbiome in the pathophysiology of mental disorders, four mental disorders were identified: Alzheimer’s disease, dementia, and cognitive disorders; autism spectrum disorder; Down’s syndrome and mental retardation; and Bipolar disorders. Studies argue for correlations between oral microbiota and Alzheimer’s disease, autism spectrum disorders, Down’s syndrome, and bipolar disorders. This field is still under-studied, and studies are needed to clarify the biological links and interconnections between the oral microbiota and the pathophysiology of all mental health disorders. Researchers should focus their efforts to develop research on the oral–brain axis in the future. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)
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