Oral Microbiome in Periodontal Disease: Where Are We Now?

Alzheimer's disease and related dementias (ADRD) have been associated with alterations in both oral and gut microbiomes. While extensive research has focused on the role of gut dysbiosis in ADRD, the contribution of the oral microbiome remains relatively understudied. Furthermore, the potential synergistic interactions between oral and gut microbiomes in ADRD pathology are largely unexplored. This study aims to evaluate distinct patterns and potential synergistic effects of oral and gut microbiomes in a cohort of predominantly Hispanic individuals with cognitive impairment (CI) and without cognitive impairment (NC). We conducted 16S rRNA gene sequencing on stool and saliva samples from 32 participants (17 CI, 15 NC; 62.5% female, mean age = 70.4 ± 6.2 years) recruited in San Antonio, Texas, USA. Correlation analysis through MaAslin2 assessed the relationship between participants' clinical measurements (e.g., fasting glucose and blood cholesterol) and their gut and saliva microbial contents. Differential abundance analysis evaluated taxa with significant differences between CI and NC groups, and alpha and beta diversity metrics assessed within-sample and group compositional differences. Our analyses revealed no significant differences between NC and CI groups in fasting glucose or blood cholesterol levels. However, a clear association was observed between gut microbiome composition and levels of fasting glucose and blood cholesterol. While alpha and beta diversity metrics showed no significant differences between CI and NC groups, differential abundance analysis revealed an increased presence of oral genera such as Dialister , Fretibacterium , and Mycoplasma in CI participants. Conversely, CI individuals exhibited a decreased abundance of gut genera, including Shuttleworthia , Holdemania , and Subdoligranulum , which are known for their anti-inflammatory properties. No evidence was found for synergistic contributions between oral and gut microbiomes in the context of ADRD. Our findings suggest that similar to the gut microbiome, the oral microbiome undergoes significant modifications as individuals transition from NC to CI. Notably, the identified oral microbes have been previously associated with periodontal diseases and gingivitis. These results underscore the necessity for further investigations with larger sample sizes to validate our findings and elucidate the complex interplay between oral and gut microbiomes in ADRD pathogenesis.

Oral infection with a periodontal pathogen alters oral and gut microbiomes

Elderly subjects with more than 20 natural teeth have a higher healthy life expectancy than those with few or no teeth. The oral microbiome and its metabolome are associated with oral health, and they are also associated with systemic health via the oral-gut axis. Here, we analyzed the oral and gut microbiome and metabolome profiles of elderly subjects with more than 26 natural teeth. Salivary samples collected as mouth-rinsed water and fecal samples were obtained from 22 healthy individuals, 10 elderly individuals with more than 26 natural teeth and 24 subjects with periodontal disease. The oral microbiome and metabolome profiles of elderly individuals resembled those of subjects with periodontal disease, with the metabolome showing a more substantial differential abundance of components. Despite the distinct oral metabolome profiles, there was no differential abundance of components in the gut microbiome and metabolomes, except for enrichment of short-chain fatty acids in elderly subjects. Finally, to investigate the relationship between the oral and gut microbiome and metabolome, we analyzed bacterial coexistence in the oral cavity and gut and analyzed the correlation of metabolite levels between the oral cavity and gut. However, there were few associations between oral and gut for bacteria and metabolites in either elderly or healthy subjects. Overall, these results indicate distinct oral microbiome and metabolome profiles, as well as the lack of an oral-gut axis in elderly subjects with a high number of natural teeth.

This comprehensive review of the literature aimed to investigate the interplay between the oral microbiome, oral cavity conditions, and host immune response in Diabetes mellitus (DM). Moreover, this review also aimed to investigate how DM related risk factors, such as advanced age, hyperglycemia, hyperlipidemia, obesity, hypertension and polycystic ovary syndrome (PCOS), act in promoting or modifying specific mechanisms that could potentially perpetuate both altered systemic and oral conditions. We found that poorly controlled glycemic index may exert a negative effect on the immune system of affected individuals, leading to a deficient immune response or to an exacerbation of the inflammatory response exacerbating DM-related complications. Hyperglycemia induces alterations in the oral microbiome since poor glycemic control is associated with increased levels and frequencies of periodontal pathogens in the subgingival biofilm of individuals with DM. A bidirectional relationship between periodontal diseases and DM has been suggested: DM patients may have an exaggerated inflammatory response, poor repair and bone resorption that aggravates periodontal disease whereas the increased levels of systemic pro-inflammatory mediators found in individuals affected with periodontal disease exacerbates insulin resistance. SARS-CoV-2 infection may represent an aggravating factor for individuals with DM. Individuals with DM tend to have low salivary flow and a high prevalence of xerostomia, but the association between prevalence/experience of dental caries and DM is still unclear. DM has also been associated to the development of lesions in the oral mucosa, especially potentially malignant ones and those associated with fungal infections. Obesity plays an important role in the induction and progression of DM. Co-affected obese and DM individuals tend to present worse oral health conditions. A decrease in HDL and, an increase in triglycerides bloodstream levels seem to be associated with an increase on the load of periodontopathogens on oral cavity. Moreover, DM may increase the likelihood of halitosis. Prevalence of impaired taste perception and impaired smell recognition tend to be greater in DM patients. An important interplay among oral cavity microbiome, DM, obesity and hypertension has been proposed as the reduction of nitrate into nitrite, in addition to contribute to lowering of blood pressure, reduces oxidative stress and increases insulin secretion, being these effects desirable for the control of obesity and DM. Women with PCOS tend to present a distinct oral microbial composition and an elevated systemic response to selective members of this microbial community, but the association between oral microbiome, PCOS are DM is still unknown. The results of the studies presented in this review suggest the interplay among the oral microbiome, oral cavity conditions, host immune response and DM and some of the DM associated risk factors exist. DM individuals need to be encouraged and motivated for an adequate oral health care. In addition, these results show the importance of adopting multidisciplinary management of DM and of strengthening physicians-dentists relationship focusing on both systemic and on oral cavity conditions of DM patients.

Alterations in both oral and gut microbiomes have been associated with Alzheimer’s disease and related dementia (ADRD). While extensive research has focused on the role of gut dysbiosis in ADRD, the contribution of the oral microbiome remains relatively understudied. This study aims to evaluate distinct patterns and potential synergistic effects of oral and gut microbiomes in a cohort of predominantly Hispanic individuals with cognitive impairment (CI) and without cognitive impairment (NC). We conducted 16S rRNA gene sequencing on stool and saliva samples from 32 participants (17 CI, 15 NC; 62.5% female, mean age = 70.4 ± 6.2 years) recruited in San Antonio, Texas, USA. Differential abundance analysis evaluated taxa with significant differences between both groups. While diversity metrics showed no significant differences between CI and NC groups, differential abundance analysis revealed an increased presence of oral genera such as Dialister, Fretibacterium, and Mycoplasma in CI participants. Conversely, CI individuals exhibited a decreased abundance of gut genera, including Shuttleworthia, Holdemania, and Subdoligranulum, which are known for their anti-inflammatory properties. No evidence was found for synergistic contributions between oral and gut microbiomes in the context of CI. Our findings suggest that like the gut microbiome, the oral microbiome of CI participants undergoes significant modifications. Notably, the identified oral microbes have been previously associated with periodontal diseases and gingivitis. These results underscore the necessity for further investigations with larger sample sizes to validate our findings and elucidate the complex interplay between oral and gut microbiomes in ADRD pathogenesis.

Background:Periodontal Disease (PD) has been recurrently linked with Rheumatoid Arthritis (RA) physiopathogenesis, from dysbiosis of oral microbiome (OM) to auto-antibody development and citrullinization.1 Moreover, PD is strongly attached with aging...

Background:Oral microbiome (OM) seems to be significant in the pathogenesis of some immune-mediated diseases, such as rheumatoid arthritis (RA), psoriasis or inflammatory bowel disease.1 Some microorganisms, as Porphyromonas gingivalis have been related with the production of autoantibodies. Also it has been suggested that composition of OM could change RA disease course, being more difficult-to-treat and having higher disease activity scores.2Objectives:To identify which variables could predict the appearance of altered OM and its implications in clinical practice.Methods:Patients were recruited if they were diagnosed of RA and were at active treatment (biological, classical or targeted synthetic disease modifying anti-rheumatic drugs [b/cs/tsDMARDs]). Patients performed a dental review with a specialized odontologist that made an OM test (semiquantitative PCR), and oral health standards were instructed (following criteria of American Academy of Periodontology). Recruitment was made during 2020 in the Clinical University Hospital in Santiago de Compostela, Spain. Disease activity reevaluation was made 2 months later.Treatment, demographic and clinical data were collected from participants.Univariable logistic and linear regression were performed to identify predictors of OM. Variables with p<0.20 were selected for multivariable analysis.Stata 15.1 was used to perform statistical analysis.Results:47 patients were selected of whom 40 were female. Mean age was 55.43 years (SD 14.42). 30.77% were current or ex-smokers. Mean time since RA diagnosis was 14.89 years (SD 8.47). 63.83% were anti-citrullinated peptide autoantibody (ACPA) positive and 70.21% were rheumatoid factor (RF) positive, letting only 6 patients double negative. 46.81% had moderate/severe periodontal disease (PD). 32.61% of patients had any comorbidity. Mean DAS28 at the OM test was 2.67 (SD 1.28) and after 2 months 2.37 (SD 1.03). Mean C-reactive protein (CRP) was 0.64 mg/dl (SD 1.48) and median erythrocyte sedimentation rate (ESR) was 13 mm (IQR 7;27). All patients were under glucocorticoid treatment, 46 with bDMARD, 1 with tsDMARD and 46 with csDMARD. Treponema denticola was detected in 44.68% of patients, P. gingivalis in 29.79%, Actinomyces spp in 8.51%, Tanerella forsythia in 36.17% and Prevotella intermedia in 25.53%. Only 15 patients were full-negative for OM test.Univariable analysis identified RF positive, double autoantibody positive (RF and ACPA) and moderate/severe PD as potential predictors of the presence of at least one oral microorganism (p<0.20). Multivariable testing pointed out moderate/severe PD as predictor of the presence of at least one oral microorganism (OR 22.91 [CI95% 2.38-220.4] p=0.007).Univariable analysis identified higher age, presence of any comorbidity, RF positive, higher CRP, treatment with anti-tumour necrosis alpha (aTNF) and moderate/severe PD as potential predictors of the presence of multiple species in OM (p<0.20). Multivariable testing pointed out moderate/severe PD as predictor of the presence of multiple species in OM (ß 0.39 [95%CI 0.19-0.58] p=0.000).Conclusion:Oral microbiome is closely related with periodontal disease, added to our results, a relationship between OM and disease activity has been exposed. In this analysis the role of OM and autoantibody profile is manifest, as being double positive or RF positive is associated with the presence of altered OM. Also patients with high acute-phase reactants, active disease and under aTNF treatment could delineate a specific RA population under risk of altered OM, where intensive strategies for changing oral microbiome could have any repercussion in the disease course.

The oral cavity microbiome comprises benign and pathogenic bacteria, with more than 700 species identified. However, the current literature regarding resident bacterial flora in the oropharyngeal cavities in cleft lip/palate (CLP) patients still needs to be completed. This review aims to evaluate the role of the oral microbiome of cleft patients as an indicator in systemic diseases for which cleft patients might be at higher risk in the short or long term. A literature review was performed in July 2020 using Biomedical Reference Collection Comprehensive, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, Dentistry & Oral Sciences Source via Elton B. Stephens Company/Online Database (EBSCO), Turning Research into Practice (TRIP), and PubMed. The keywords used were "oral, bacteria, microbiome, biota, flora, cleft, palate." The resulting 466 articles were deduplicated using Endnote. The total amount of articles' abstracts without duplicates was filtered using a set criterion. The title and abstract filter criteria included 1) cleft lip (CL) and/or cleft palate (CP) patients, 2) changes in the oral microbiome in CL and/or CP patients, 3) male and female patients 0-21 years old, and 4) English language. The full-text filter criteria included 1) CL and/or CP patients vs. non-cleft control patients, 2) oral bacteria, 3) nonprocedural measurements of microorganisms, and 4) case-control studies. A Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flow chart was created using the EndNote data results. The final five articles of the systematic search indicated that the oral cavity of cleft lip and/or palate patients resulted in 1) contradicting levels of Streptococcus mitis and Streptococcus salivarius; 2) lower levels of Streptococcus gordonii, Bordetella dentium, Fusobacterium nucleatum, Veillonella parvula, Bacillus and Lautropia when compared to the control group; 3) higher levels of Staphylococcus epidermidis and Methicillin-sensitive Staphylococcus aureus compared to the control group; 4) presence of Enterobacter cloacae 36.6%, Klebsiella pneumoni 53.3%, and Klebsiella oxytoca 76.6%vs. absence in the control non-cleft group. Patients with CL and/or CP are at higher risk for caries, periodontal diseases, and upper and lower respiratory infections. The results from this review indicate that relative levels of certain bacteria may be associated with these issues. The lower levels of S. mitis, S. salivarius, S. gordini, and F. nucleatum in the oral cavity of cleft patients could be linked as a possible cause of the higher incidence of tooth decay, gingivitis and periodontal disease as high levels of these bacteria are associated with oral disease. Further, the higher incidence of sinusitis in cleft patients might be linked to low levels of S. salivarius in the oral profile of these patients. Likewise, E. cloacae, K. oxycota, and K. pneumoni have been linked with pneumonia and bronchiolitis, both of which are increased in cleft patients. The oral bacterial dysbiosis of cleft patients observed in this review may play a vital function in the oral microbiome's diversity, which could play a role in disease progression and disease markers. The pattern seen in cleft patients potentially demonstrates how structural abnormalities can lead to the onset of severe infection.

This study aimed to comprehensively analyze the microbiome of dental plaque in individuals with varying periodontal statuses, encompassing both periodontal health and disease. The primary objectives were to identify microbial markers associated with different clinical conditions, explore variations in microbial diversity, and investigate potential correlations between the oral microbiome and clinical parameters. A cross-sectional design was employed, involving 164 participants aged 18 to 65 years. Inclusion criteria comprised individuals with good oral and systemic health for the periodontal health group and those diagnosed with various stages of periodontal disease for the periodontal disease group. Dental plaque samples were meticulously collected from diverse tooth surfaces, and clinical examinations were conducted to assess periodontal health status. High-throughput sequencing of the 16S ribosomal RNA (rRNA) gene was utilized for microbiome analysis. Demographic characteristics revealed a balanced distribution between the periodontal health and disease groups. Clinical parameters, including probing depth, clinical attachment loss, and bleeding on probing, exhibited significant differences between the two groups (p < 0.001). Microbial diversity indices indicated a higher diversity in the periodontal health group compared to the disease group (p < 0.001). Analysis of relative abundance of bacterial phyla identified significant variations, with Firmicutes, Bacteroidetes, and Actinobacteria showing differential prevalence between health and disease (p < 0.05). Differentially abundant taxa analysis highlighted specific species associated with each clinical condition, including Prevotella intermedia and Porphyromonas gingivalis. Network analysis revealed complex microbial interactions within the oral microbiome. Functional predictions indicated variations in metabolic capabilities between health and disease, with potential implications for virulence and antibiotic resistance. This study provides a comprehensive analysis of the oral microbiome in periodontal health and disease, revealing significant associations between microbial composition and clinical parameters. The identification of microbial markers and functional insights enhances our understanding of the complex interplay within the oral ecosystem. These findings hold promise for advancing diagnostic and therapeutic approaches tailored to individual microbial profiles.

Exploring the intricate interplay between two prevalent chronic conditions, diabetes mellitus and periodontal disease, reveals a bidirectional relationship. Recent evidence underscores the pivotal influence of the microbiome, particularly the gut and oral microbiome, in shaping the pathogenesis of both diabetes and periodontal disease. The present comprehensive review aimed to elucidate the current understanding of how these microbial communities contribute to the development and progression of diabetes, especially when compounded by periodontal disease. However, emerging evidence suggests a complex bidirectional relationship between these two conditions. The microbiome’s involvement in these conditions unfolds through multifaceted mechanisms, with microbial dysbiosis influencing systemic inflammation, insulin resistance, and periodontal tissue degradation. The authors explored the dynamic crosstalk between the gut and oral microbiome, shedding light on how alterations in these microbial ecosystems may exacerbate the interconnected manifestations of diabetes and periodontal disease. Furthermore, present review unraveled the potential therapeutic implications for targeted interventions. By dissecting the microbiome-driven pathways, authors identified the promising avenues for precision medicine and tailored therapies. This exploration opens new vistas for developing strategies that leverage the microbiome to mitigate the impact of diabetes with periodontal disease. As the authors navigated this complex terrain, the manuscript underscores the urgency of a holistic understanding and targeted modulation of the microbiome to revolutionise treatment paradigms for these intertwined chronic conditions. The present manuscript aimed to review the current understanding of the role of the gut and oral microbiome in the development and progression of diabetes with periodontal disease.

BackgroundPeriodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts.MethodsIn the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD.ResultsSignificantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments.ConclusionThis study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes.

The oral microbiome in dogs is a complex community. Under some circumstances, it contributes to periodontal disease, a prevalent inflammatory disease characterized by a complex interaction between oral microbes and the immune system. Porphyromonas and Tannerella spp. are usually dominant in this disease. How the oral microbiome community is altered in periodontal disease, especially sub-dominant microbial populations is unclear. Moreover, how microbiome functions are altered in this disease has not been studied. In this study, we compared the composition and the predicted functions of the microbiome of the cavity of healthy dogs to those with from periodontal disease. The microbiome of both groups clustered separately, indicating important differences. Periodontal disease resulted in a significant increase in Bacteroidetes and reductions in Actinobacteria and Proteobacteria. Porphyromonas abundance increased 2.7 times in periodontal disease, accompanied by increases in Bacteroides and Fusobacterium. It was predicted that aerobic respiratory processes are decreased in periodontal disease. Enrichment in fermentative processes and anaerobic glycolysis were suggestive of an anaerobic environment, also characterized by higher lipopolysaccharide biosynthesis. This study contributes to a better understanding of how periodontal disease modifies the oral microbiome and makes a prediction of the metabolic pathways that contribute to the inflammatory process observed in periodontal disease.

Bariatric Surgery Alters Oral Microbiome: Evidence From Obese Patients and a Mouse Model

Despite known links between oral health and dementia and the growing understanding of the role of the human microbiome in health, few studies have explored the relationship between the oral microbiome and cognition. Additionally, there is a notable absence of research on how the oral microbiome is associated with cognitive function in Black adult caregivers of cancer patients despite their elevated risk for both oral disease and cognitive impairment. This study aimed to characterize the oral microbiome of Black caregivers of people living with cancer and explore the association of the oral microbiome with cognitive performance. Thirty-one self-identified Black or African American caregivers of cancer patients in the greater metropolitan Atlanta area participated in the study. They provided oral microbiome samples. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA), depressive symptoms with the Center for Epidemiological Studies-Depression Scale, and individual race-related stress with the Index of Race-Related Stress-Brief. Salivary microbiome diversity was analyzed using alpha and beta diversity metrics, and taxa associated with cognition were identified through differential abundance testing, adjusting for potential confounders. The mean age of participants was 54.8 years. MoCA scores ranged from 18 to 30, with a mean of 25. Participants were categorized into normal cognition (MoCA ≥ 26, n = 12) and low cognition (MoCA < 26, n = 16) groups. Education level and individual race-related stress were associated with cognition group and were controlled for in the oral microbiome analysis. Alpha and beta diversity analyses showed no significant overall differences between cognition groups. Differential abundance testing suggested 48 taxa were associated with cognition status, many of which are known to be associated with periodontal disease and cognition. This study revealed associations between cognition status and specific oral bacteria, many of which are known to be associated with periodontal disease and cognitive impairment. These findings underscore the complex relationship between oral health and cognitive function, suggesting a need for further research to develop oral microbiome profiles capable of identifying individuals at risk for cognitive decline and guiding targeted interventions for promoting overall well-being and cognitive health.

Introduction and objective: Periodontitis (PD) is caused by dysbiosis of the oral microbiome (OMB). The prevalence of PD is increased in RA patients. Both conditions have the ability to activate common inflammatory pathways. The OMB shift contributes to more severe course of PD and RA. This paper aims to summarize the impact of OMB on chronic inflammation in the pathogenesis of PD and RA. Description of the state of knowledge: The OMB can influence chronic inflammation and protein citrullination. The presence of antibodies against citrullinated peptides (ACPA) correlates with an increased incidence and severity of periodontitis. While numerous studies have reported a relationship between the OMB, PD and RA, the role of specific bacteria in RA remains unclear. Methodology: A literature review was conducted using two databases - PubMed and Google Scholar - with search terms such as "oral microbiome”, “rheumatoid arthritis", "periodontal health”, “oral microbiota”, “periodontal disease”. Articles published within the last eight years were prioritized. Conclusions: PD is more prevalent and severe particularly in ACPA-positive RA patients. Alterations in OMB are associated with systemic inflammation, contributing to RA progression. and worsening periodontal conditions. Periodontal treatment shows a potential to reduce RA activity, emphasizing the importance of dental care in RA. Anti-inflammatory treatments may restore oral homeostasis. Targeting the OMB offers a potential for managing RA and PD. Further research is needed to establish guidelines for personalized therapies and prophylaxis.