The Obesity–Periodontitis Axis: Microbial Mechanisms and Clinical Implications

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Exploring the Potential of Breast Microbiota as Biomarker for Breast Cancer and Therapeutic Response

Can oral pathogens influence allergic disease?

Background: Alteration of the oral microbiome (microbial dysbiosis) with cigarette smoking is well established. However, the effect of electronic cigarettes (e-cigs) use on the oral microbiome is unknown, although there are emerging data that e-cigs induce microbial changes similar to smoking. In smoking-related diseases, such as chronic obstructive pulmonary disease, there are changes in the oral microbiome and in the expression of genes involved in inflammatory pathways. Similar to the oral microbiome, it is feasible that smoking tobacco and e-cig use could also affect the lung microbiome. To the best of our knowledge, there is only one published study investigating smoking tobacco effects on the oral and lung microbiome. No published studies have evaluated concurrent effects of e-cigs in the oral and lung microbiome. Aims: We hypothesize that microbial dysbiosis and expression of inflammatory cytokines in the oral cavity and lung will differ between smokers and nonsmokers, and that e-cig users will have microbial dysbiosis more similar to smokers. To accomplish this, we propose 1) to examine the association of oral and lung microbiome in nonsmokers, smokers and e-cig users, 2) to determine if the oral microbiome and the lung microbiome differ among these groups, and 3) to determine correlation of the microbiota with host expression of inflammation-related genes. Methods: A cross-sectional study using bronchoscopy and oral rinse collection of 10 never-smokers, 8 cigarette smokers, and 10 e-cig users was conducted. For each study participant, RNA was extracted from saliva and bronchoalveolar lavage (BAL) samples for total transcriptome analysis using RNA-seq; facilitating this approach allows measurement of bacterial communities and human inflammatory cytokine expression in the same assay. To determine microbial dysbiosis by smoking status, the Mann Whitney U-test and Kruskal-Wallis H-test were used with Bonferroni correction for multiple comparisons. Both effect size (fold change >1.5) and adjusted p-value cutoffs (<0.05) were used to identify statistical significance. Results: In preliminary analyses we identified 2,257 bacterial strains in saliva samples and 1592 in BAL samples. We found a lack of concordance of highly abundant bacteria in the oral cavity and lungs. The top twenty expressed human genes were associated with RNA splicing, RNA elongation and miRNAs. Comparisons of microbial dysbiosis by smoking status are currently under way. Conclusion: The composition of the microbiome for saliva is different from that of BAL. Comparison of the metatranscriptome and transcriptome between the lung and oral cavity, as well as between smokers, nonsmokers and e-cigarette users, will allow us to observe how e-cig use compares with cigarette smoking and never smoking in terms of microbial dysbiosis and inflammatory cytokines. Citation Format: Kevin L. Ying, Min-Ae Song, Daniel Y. Weng, Quentin A. Nickerson, Joseph P. McElroy, David Frankhouser, Pearlly S. Yan, Ralf Bundschuh, Theodore M. Brasky, Mark D. Wewers, Ewy Mathé, Jo L. Freudenheim, Peter G. Shields. Using oral and lung microbiome to assess microbial dysbiosis and inflammatory response to electronic cigarettes and to cigarettes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1231.

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.

Breast cancer and periodontitis, potentially related conditions affects millions worldwide . Latest research reveals that both the diseases share common pathways and these play a critical role in the development , progression and treatment of both conditions . Periodontitis , a chronic progressive inflammatory disease of the periodontium is being highlighted for its incrimination in causing various systemic diseases . The aim of this article is to put light onto all probable pathways that makes periodontal inflammation a risk factor for Breast cancer .. This article draws attention to the commonalities shared by the two diseases, in the context of chronic inflammation , microbial dysbiosis and immunological pathways in the initiation and progression of breast cancer . It emphasizes the role of multifaceted research to reveal the underlying pathways seen in this association . The inflammatory microenvironment seen in periodontitis mimics the microenvironment that brings about the process of oncogenesis in breast cancer . Crucial bacterial species intertwined in periodontitis, like Fusobacterium nucleatum and Porphyromonas gingivalis, are seen within breast cancer tissues, indicating a possible etiological link through bacteremia and later metastatic colonization . The inflammatory terrain specific of periodontitis, rich in cytokines, prostaglandins, and interleukins, simulates the inflammatory environment that promotes oncogenesis in breast tissue . Inheritable tendencies and hormonal influences, particularly estrogen metabolism intermediated by oral and gut microbiota, further intertwine these conditions . Elevated C- reactive protein situations, a marker of systemic inflammation seen in periodontitis, are also associated with increased breast cancer threat . Research indicates that elevated levels of molecules like RANK and its ligand RANKL may promote progression and metastasis in breast cancer . A comprehension of these pathways that link Periodontitis to breast cancer can offer beneficial awareness for developing preventive and curative strategies, if proven . Such knowledge could lead to innovative interventions targeting inflammatory processes potentially mitigating the risk and progress of the two diseases . After going through various available literature it could be said that periodontal pathogens might influence breast cancer either directly or through systemic inflammatory pathways . While some evidence hints at a possible link between periodontitis and breast cancer . Databases including PubMed , PubMed Central and ResearchGate were searched for articles yielding 32 relevant English articles between 2016 to 2023, which had one of the keywords of “Periodontal Disease” , “Breast cancer” , “Inflammation” and “Myeloid derived Suppressor cells” in their titles . A total of 13 English articles were selected by the researcher for final analysis.

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.

To the Editor: Because epidemiological evidence supports an association between cardiovascular and periodontal disease, we assessed whether periodontal pathogens were present in atherosclerotic lesions. To detect invasive bacteria, the natural tropism of the bacteria toward human tissues was exploited. Further, bacterial presence was demonstrated using quantitative polymerase chain reaction (Q-PCR). This confirms the presence of periodontal pathogens in atherosclerotic lesions, whereby the bacteria could contribute to the vascular pathology either directly through their cytotoxicity or indirectly by inducing or exacerbating inflammation. Cardiovascular disease (CVD) is the leading cause of death in the in the United States.1 According to the American Heart Association’s statistics from 2003, there were no previous symptoms in 50% of men and 63% of women who died suddenly from CHD. In a 10-year follow-up study, ≈25% of coronary deaths in males and 15% in females occurred in persons in the lowest two quintiles of the multivariate Framingham Heart Study risk scores.2 This and other data have led to an emerging paradigm shift from coronary heart disease having a purely hereditary/nutritional causation to possibly having an infectious component.3 Many epidemiological studies strongly suggest that periodontitis may be a risk factor for coronary heart disease (CHD).4 Serologically, edentulousness and serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in 1163 men were recently shown to be associated with CHD.5 In a larger prospective study of 6950 subjects, the same authors provide serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.6 Previous studies have identified 16S rRNA of oral microbial pathogens, including P gingivalis and A actinomycetemcomitans , …

Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = -0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia-Shigella and the lower abundance of Methylobacterium-Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and "healthy" controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.

When specific gut microbes reveal a possible link between hepatic steatosis and adipose tissue

Role of oral and gut microbiome in nitric oxide-mediated colon motility

Oral infection with a periodontal pathogen alters oral and gut microbiomes

BackgroundOral and gut microbiomes have been associated with Alzheimer’s disease and related dementias (ADRD). Although the role of the gut microbiome and gut dysbiosis in ADRD has been extensively studied, research on the oral microbiome is lacking. Moreover, the synergetic contribution of oral and gut microbiomes to ADRD is unexplored. This study aimed to assess the differential patterns of oral and gut microbiomes and their synergetic effects in patients with mild cognitive impairment (MCI) compared to normal cognition (NC).MethodGut and saliva microbiome abundance and diversity measurements were obtained using 16S rRNA gene sequencing of stool and saliva samples from 27 participants (12 MCI, 15 NC, %F = 66.7, Age = 70.2 ± 6.4) recruited in San Antonio, Texas, USA (Table 1). The indexes Chao1, ACE, Observe, Shannon, and Simpson were computed to assess the 〈‐diversity of samples. However, the ®‐diversity was investigated after carrying out the principal coordinates analysis (PCoA) based on Bray‐Curtis distances to visualize group separation in compositional data. We used linear discriminant effect size and differential abundant analysis to identify gut and saliva features statistically different between MCI and NC (adjusted p‐value &lt; 0.005).ResultNo differences in bacteria 〈‐ and ®‐diversity between MCI and NC (Figure 1) were found. However, we found an increased abundance of oral pathogenic genera, including Anaeroglobus, Centipeda, Cardiobacterium, Dialister, Fretibacterium, Leptotrichia, Mycoplasma, Tannerella, and Treponema in patients with MCI (Figure 2). We also found that MCI patients have a decreased abundance of gut genera Butyricicoccus, Defluviitaleaceae, Lachnospira, Paludicola, Shuttleworthia, and Subdoligranulum. These differential abundant gut genera have been shown to harbor anti‐inflammatory properties. We did not find evidence of synergetic contributions of oral and gut genera to MCI.ConclusionOur results suggest that the saliva microbiome, like the gut microbiome, is disrupted as patients progress from NC to MCI. The pathogenic oral microbes we found were previously linked to periodontal and gingivitis pathogens. Further studies with larger sample sizes are needed to validate these findings.

ST-segment elevation myocardial infarction (STEMI) is characterized by thrombotic coronary artery occlusions caused by atherosclerotic plaque rupture. The gut microbiome potentially contributes to the pathogenesis of coronary artery diseases. This study investigated the microbial diversity and composition of coronary thrombi in STEMI patients and the composition of the thrombus microbiome relative to that of the oral and gut microbiomes. A case–control study was performed with 22 STEMI patients and 20 age- and sex-matched healthy controls. Coronary thrombi were acquired from STEMI patients via manual thrombus aspiration during primary coronary intervention. Oral swab and stool samples were collected from both groups, and 16S rRNA sequencing and metagenomic microbiome analyses were performed. Microbial DNA was detected in 4 of 22 coronary thrombi. Proteobacteria (p) and Bacteroidetes (p) were the most abundant phyla. The oral and gut microbiomes significantly differed between patients and healthy controls. The patient group presented microbial dysbiosis, as follows: a higher relative abundance of Proteobacteria (p) and Enterobacteriaceae (f) in the gut microbiome and a lower abundance of Firmicutes (p) and Haemophilus (g) in the oral microbiome. Furthermore, 4 significantly abundant genera were observed in the coronary thrombus in the patients: Escherichia, 1.25%; Parabacteroides, 0.25%; Christensenella, 0.0%; and Bacteroides, 7.48%. The present results indicate that the relative abundance of the gut and oral microbiomes was correlated with that of the thrombus microbiome.

Protease-Activated Receptor-2 Activation: A Major Role in the Pathogenesis of Porphyromonas gingivalis Infection