Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome.

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis-these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.

Ancient Genomes From Bronze Age Remains Reveal Deep Diversity and Recent Adaptive Episodes for Human Oral Pathobionts.

Ancient microbial genomes can illuminate pathobiont evolution across millenia, with teeth providing a rich substrate. However, the characterization of prehistoric oral pathobiont diversity is limited. In Europe, only preagricultural genomes have been subject to phylogenetic analysis, with none compared to more recent archaeological periods. Here, we report well-preserved microbiomes from two 4,000-year-old teeth from an Irish limestone cave. These contained bacteria implicated in periodontitis, as well as Streptococcus mutans, the major cause of caries and rare in the ancient genomic record. Despite deriving from the same individual, these teeth produced divergent Tannerella forsythia genomes, indicating higher levels of strain diversity in prehistoric populations. We find evidence of microbiome dysbiosis, with a disproportionate quantity of S. mutans sequences relative to other oral streptococci. This high abundance allowed for metagenomic assembly, resulting in its first reported ancient genome. Phylogenetic analysis indicates major postmedieval population expansions for both species, highlighting the inordinate impact of recent dietary changes. In T. forsythia, this expansion is associated with the replacement of older lineages, possibly reflecting a genome-wide selective sweep. Accordingly, we see dramatic changes in T. forsythia's virulence repertoire across this period. S. mutans shows a contrasting pattern, with deeply divergent lineages persisting in modern populations. This may be due to its highly recombining nature, allowing for maintenance of diversity through selective episodes. Nonetheless, an explosion in recent coalescences and significantly shorter branch lengths separating bacteriocin-carrying strains indicate major changes in S. mutans demography and function coinciding with sugar popularization during the industrial period.

SARS-CoV-2, periodontal pathogens, and host factors: The trinity of oral post-acute sequelae of COVID-19.

COVID-19 as a pan-epidemic is waning but there it is imperative to understand virus interaction with oral tissues and oral inflammatory diseases. We review periodontal disease (PD), a common inflammatory oral disease, as a driver of COVID-19 and oral post-acute-sequelae conditions (PASC). Oral PASC identifies with PD, loss of teeth, dysgeusia, xerostomia, sialolitis-sialolith, and mucositis. We contend that PD-associated oral microbial dysbiosis involving higher burden of periodontopathic bacteria provide an optimal microenvironment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These pathogens interact with oral epithelial cells activate molecular or biochemical pathways that promote viral adherence, entry, and persistence in the oral cavity. A repertoire of diverse molecules identifies this relationship including lipids, carbohydrates and enzymes. The S protein of SARS-CoV-2 binds to the ACE2 receptor and is activated by protease activity of host furin or TRMPSS2 that cleave S protein subunits to promote viral entry. However, PD pathogens provide additional enzymatic assistance mimicking furin and augment SARS-CoV-2 adherence by inducing viral entry receptors ACE2/TRMPSS, which are poorly expressed on oral epithelial cells. We discuss the mechanisms involving periodontopathogens and host factors that facilitate SARS-CoV-2 infection and immune resistance resulting in incomplete clearance and risk for 'long-haul' oral health issues characterising PASC. Finally, we suggest potential diagnostic markers and treatment avenues to mitigate oral PASC.

Acquisition of the arginine deiminase system benefits epiparasitic Saccharibacteria and their host bacteria in a mammalian niche environment.

Saccharibacteria are a group of widespread and genetically diverse ultrasmall bacteria with highly reduced genomes that belong to the Candidate Phyla Radiation. Comparative genomic analyses suggest convergent evolution of key functions enabling the adaptation of environmental Saccharibacteria to mammalian microbiomes. Currently, our understanding of this environment-to-mammal niche transition within Saccharibacteria and their obligate episymbiotic association with host bacteria is limited. Here, we identified a complete arginine deiminase system (ADS), found in further genome streamlined mammal-associated Saccharibacteria but missing in their environmental counterparts, suggesting acquisition during environment-to-mammal niche transition. Using TM7x, the first cultured Saccharibacteria strain from the human oral microbiome and its host bacterium Actinomyces odontolyticus, we experimentally tested the function and impact of the ADS. We demonstrated that by catabolizing arginine and generating adenosine triphosphate, the ADS allows metabolically restrained TM7x to maintain higher viability and infectivity when disassociated from the host bacterium. Furthermore, the ADS protects TM7x and its host bacterium from acid stress, a condition frequently encountered within the human oral cavity due to bacterial metabolism of dietary carbohydrates. Intriguingly, with a restricted host range, TM7x forms obligate associations with Actinomyces spp. lacking the ADS but not those carrying the ADS, suggesting the acquired ADS may also contribute to partner selection for cooperative episymbiosis within a mammalian microbiome. These data present experimental characterization of a mutualistic interaction between TM7x and their host bacteria, and illustrate the benefits of acquiring a novel pathway in the transition of Saccharibacteria to mammalian microbiomes.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

A new approach to describe the taxonomic structure of microbiome and its application to assess the relationship between microbial niches.

BACKGROUND: Data from microbiomes from multiple niches is often collected, but methods to analyse these often ignore associations between niches. One interesting case is that of the oral microbiome. Its composition is receiving increasing attention due to reports on its associations with general health. While the oral cavity includes different niches, multi-niche microbiome data analysis is conducted using a single niche at a time and, therefore, ignores other niches that could act as confounding variables. Understanding the interaction between niches would assist interpretation of the results, and help improve our understanding of multi-niche microbiomes. METHODS: In this study, we used a machine learning technique called latent Dirichlet allocation (LDA) on two microbiome datasets consisting of several niches. LDA was used on both individual niches and all niches simultaneously. On individual niches, LDA was used to decompose each niche into bacterial sub-communities unveiling their taxonomic structure. These sub-communities were then used to assess the relationship between microbial niches using the global test. On all niches simultaneously, LDA allowed us to extract meaningful microbial patterns. Sets of co-occurring operational taxonomic units (OTUs) comprising those patterns were then used to predict the original location of each sample. RESULTS: Our approach showed that the per-niche sub-communities displayed a strong association between supragingival plaque and saliva, as well as between the anterior and posterior tongue. In addition, the LDA-derived microbial signatures were able to predict the original sample niche illustrating the meaningfulness of our sub-communities. For the multi-niche oral microbiome dataset we had an overall accuracy of 76%, and per-niche sensitivity of up to 83%. Finally, for a second multi-niche microbiome dataset from the entire body, microbial niches from the oral cavity displayed stronger associations to each other than with those from other parts of the body, such as niches within the vagina and the skin. CONCLUSION: Our LDA-based approach produces sets of co-occurring taxa that can describe niche composition. LDA-derived microbial signatures can also be instrumental in summarizing microbiome data, for both descriptions as well as prediction.

Influence of oral microbiome on longitudinal patterns of oral mucositis severity in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. METHODS: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. RESULTS: Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. CONCLUSIONS: These findings suggest the potential to personalize treatment for OM. PLAIN LANGUAGE SUMMARY: Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.

Relationship between vaginal and oral microbiome in patients of human papillomavirus (HPV) infection and cervical cancer.

BACKGROUND: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. MATERIALS AND METHODS: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. RESULTS: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. CONCLUSION: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.

Saliva­microbiome­derived signatures: expected to become a potential biomarker for pulmonary nodules (MCEPN-1).

BACKGROUND: Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cancer; however, the relationship between oral microbiota and PNs remains unknown. METHODS: We conducted a 'Microbiome with pulmonary nodule series study 1' (MCEPN-1) where we compared PN patients and healthy controls (HCs), aiming to identify differences in oral microbiota characteristics and discover potential microbiota biomarkers for non-invasive, radiation-free PNs diagnosis and warning in the future. We performed 16 S rRNA amplicon sequencing on saliva samples from 173 PN patients and 40 HCs to compare the characteristics and functional changes in oral microbiota between the two groups. The random forest algorithm was used to identify PN salivary microbial markers. Biological functions and potential mechanisms of differential genes in saliva samples were preliminarily explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups (COG) analyses. RESULTS: The diversity of salivary microorganisms was higher in the PN group than in the HC group. Significant differences were noted in community composition and abundance of oral microorganisms between the two groups. Neisseria, Prevotella, Haemophilus and Actinomyces, Porphyromonas, Fusobacterium, 7M7x, Granulicatella and Selenomonas were the main differential genera between the PN and HC groups. Fusobacterium, Porphyromonas, Parvimonas, Peptostreptococcus and Haemophilus constituted the optimal marker sets (area under curve, AUC = 0.80), which can distinguish between patients with PNs and HCs. Further, the salivary microbiota composition was significantly correlated with age, sex, and smoking history (P < 0.001), but not with personal history of cancer (P > 0.05). Bioinformatics analysis of differential genes showed that patients with PN showed significant enrichment in protein/molecular functions related to immune deficiency and energy metabolisms, such as the cytoskeleton protein RodZ, nicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) dehydrogenase, major facilitator superfamily transporters and AraC family transcription regulators. CONCLUSIONS: Our study provides the first evidence that the salivary microbiota can serve as potential biomarkers for identifying PN. We observed a significant association between changes in the oral microbiota and PNs, indicating the potential of salivary microbiota as a new non-invasive biomarker for PNs. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR2200062140; Date of registration: 07/25/2022.

Characteristics of the oral and gastric microbiome in patients with early-stage intramucosal esophageal squamous cell carcinoma.

BACKGROUND: Oral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC). METHOD: A total of 104 samples were collected from 31 patients with EIESC and 21 healthy controls. The compositions of oral and gastric microbiota were analyzed using 16 S rRNA V3-V4 amplicon sequencing. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. The correlation between oral microbiota and clinicopathological factors was evaluated using Spearman correlation analysis. Additionally, co-occurrence networks were established and random forest models were utilized to identify significant microbial biomarkers for distinguishing between the EIESC and control groups. RESULTS: A total of 292 oral genera and 223 species were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar. CONCLUSION: Our study potentially indicates that the dysbacteriosis of both the oral and gastric microbiome was associated with EIESC. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of EIESC. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563).

The complement system as a key modulator of the oral microbiome in health and disease.

In this review, we address the interplay between the complement system and host microbiomes in health and disease, focussing on oral bacteria known to contribute to homeostasis or to promote dysbiosis associated with dental caries and periodontal diseases. Host proteins modulating complement activities in the oral environment and expression profiles of complement proteins in oral tissues were described. In addition, we highlight a sub-set of bacterial proteins involved in complement evasion and/or dysregulation previously characterized in pathogenic species (or strains), but further conserved among prototypical commensal species of the oral microbiome. Potential roles of these proteins in host-microbiome homeostasis and in the emergence of commensal strain lineages with increased virulence were also addressed. Finally, we provide examples of how commensal bacteria might exploit the complement system in competitive or cooperative interactions within the complex microbial communities of oral biofilms. These issues highlight the need for studies investigating the effects of the complement system on bacterial behaviour and competitiveness during their complex interactions within oral and extra-oral host sites.

Inhaler Steroid Use Changes Oral and Airway Bacterial and Fungal Microbiome Profile in Asthma Patients.

INTRODUCTION: The full spectrum of bacterial and fungal species in adult asthma and the effect of inhaled corticosteroid use is not well described. The aim was to collect mouthwash and induced sputum samples from newly diagnosed asthma patients in the pretreatment period and in chronic asthma patients while undergoing regular maintenance inhaled corticosteroid therapy, in order to demonstrate the bacterial and fungal microbiome profile. METHODS: The study included 28 asthmatic patients on inhaler steroid therapy, 25 steroid-naive asthmatics, and 24 healthy controls. Genomic DNA was isolated from induced sputum and mouthwash samples. Analyses were performed using bacterial primers selected from the 16S rRNA region for the bacterial genome and "panfungal" primers selected from the 5.8S rRNA region for the fungal genome. RESULTS: Dominant genera in mouthwash samples of steroid-naive asthmatics were Neisseria, Haemophilus, and Rothia. The oral microbiota of asthmatic patients on inhaler steroid treatment included Neisseria, Rothia, and Veillonella species. Abundant genera in induced sputum samples of steroid-naive asthma patients were Actinomyces, Granulicatella, Fusobacterium, Peptostreptococcus, and Atopobium. Sputum microbiota of asthma patients taking inhaler steroids were dominated by Prevotella and Porphyromonas. Mucor plumbeus and Malassezia restricta species were abundant in the airways of steroid-naive asthma patients. Choanephora infundibulifera and Malassezia restricta became dominant in asthma patients taking inhaled steroids. CONCLUSION: The oral and airway microbiota consist of different bacterial and fungal communities in healthy and asthmatic patients. Inhaler steroid use may influence the composition of the oral and airway microbiota.

The Obese Taste Bud study: Objectives and study design.

AIMS: Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. MATERIALS AND METHODS: Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. RESULTS: Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. CONCLUSION: Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Differences in maternal subgingival microbiome between preterm and term births: The MOHEPI study.

AIM: Periodontitis is a potential risk factor for preterm birth (PTB) in women; however, the causal relationship or the exact mechanism remain unknown. This study aimed to compare the oral microbiome features of mothers with full-term birth (FTB) with those who had preterm delivery. METHODS: This study prospectively enrolled 60 women (30 mothers with PTB and 30 mothers with FTB), and subgingival plaque samples were collected and analysed by metagenomic 16S rDNA sequencing. Clinical measurements, including periodontal probing depth, clinical attachment level, modified gingival index (mGI) and plaque index, were performed to determine the periodontal state of the participants. Medical and obstetric data were collected as well. RESULTS: Among the periodontal measurements, mGI score, reflecting the level of gingival inflammation, exhibited a statistically significant association with PTB (adjusted odds ratio 2.705, 95% confidence interval 1.074-6.811, p = .035). When subgroup analysis was conducted based on mean mGI scores (mGI ≥ 2, high inflammation [HI] versus mGI < 2, low inflammation [LI]), microbiome analysis revealed clear distinctions in microbial compositions between PTB and FTB mothers in both the HI and LI groups. Especially in the HI group, alpha diversity exhibited a decreasing trend in PTB mothers compared to FTB mothers. Beta diversity also revealed significant differences between the two groups. In Linear Discriminant Analysis Effect Size analysis, certain anaerobic taxa, including the genera Spirochaetes, Treponema and Porphyromonas, were relatively abundant in the FTB/HI group, whereas the PTB/HI group showed a high abundance of the order Actinomycetales. Network analysis showed that the FTB/HI had relatively stronger connectivity in microbial composition than the PTB/HI group. Dysbiosis ratio of plaque microbiome, in terms of periodontitis, was significantly lower in PTB/HI group compared to FTB/HI group. CONCLUSION: The compositions of maternal subgingival microbiomes differed between PTB and FTB mothers in both the high and low levels of gingival inflammation groups. In the presence of high level of gingival inflammation, dysbiosis in plaque microbiome, in terms of periodontitis, was decreased in PTB mothers compared to FTB mothers.

Unveiling the Hidden Links: Periodontal Disease, Fusobacterium Nucleatum, and Cancers.

PURPOSE OF REVIEW: Fusobacterium nucleatum (F. nucleatum), an anaerobic, gram-negative microbe, commonly found in human dental biofilm and the gut flora. It has long been known to have a higher concentration in periodontal disease and has recently been implicated in both oral and distant cancers such as colorectal, gastrointestinal, esophageal, breast, pancreatic hepatocellular, and genitourinary cancers. However, the mechanism of its involvement in the development of cancer has not been fully discussed. This review aims to cover biological molecular and clinical aspects of F. nucleatum and cancers. RECENT FINDINGS: Studies indicate F. nucleatum promotes tumor development through chronic inflammation, immune evasion, cell proliferation activation, and direct cell interactions, as in oral squamous cell carcinoma (OSCC). In colorectal cancer (CRC), F. nucleatum contributes to tumorigenesis through ß-catenin signaling and NF-κB activation. It also induces autophagy, leading to chemoresistance in CRC and esophageal cancers, and enhances tumor growth and metastasis in breast cancer by reducing T-cell infiltration. F. nucleatum is linked to carcinogenesis and increased bacterial diversity in OSCC, with improved oral hygiene potentially preventing OSCC. F. nucleatum triggers cancer by causing mutations and epigenetic changes through cytokines and reactive oxygen species. It also promotes chemoresistance in CRC. F. nucleatum may potentially serve as a diagnostic tool in various cancers, with non-invasive detection methods available. Further investigation is needed to discover its potential in the diagnosis and treatment of OSCC and other cancers.

Longitudinal Influence of Prescribed Antidepressants on Fecal and Oral Microbiomes Among Veterans With Major Depressive Disorder.

OBJECTIVE: The purpose of this study was to evaluate the influence of a new course of antidepressant monotherapy on gut and oral microbiomes and the relationship to depressive symptoms. METHODS: Longitudinal microbiome samples obtained from 10 U.S. veterans were analyzed. Baseline samples were taken before a new course of antidepressant monotherapy (either switching from a previous treatment or starting a new treatment). Targeted genomic sequencing of the microbiome samples was used to analyze changes in taxonomy and diversity across participants, medications, and medication class. Associations between these changes and Patient Health Questionnaire-9 (PHQ-9) scores were analyzed. RESULTS: Taxonomic variability was observed across participants, with the individual being the main microbial community driver. In terms of the fecal microbiome, antidepressants were associated with shifts toward Bacteroides being less abundant and Blautia, Pseudomonas, or Faecalibacterium being more abundant. Likewise, the composition of the oral microbiome was variable, with individual participants being the primary drivers of community composition. In the oral samples, the relative abundance of Haemophilus decreased after antidepressants were started. Increases in Blautia and decreases in Bacteroides were associated with lower PHQ-9 scores. CONCLUSIONS: Antidepressants were found to influence fecal and oral microbiomes such that a new course of antidepressant monotherapy was associated with taxonomic alterations toward healthier states in both fecal and oral microbiomes, which were associated with decreases in depressive symptoms. Additional longitudinal research is required to increase understanding of microbiomes and symptom-based changes, with a particular focus on potential differences between medication classes and underlying mechanisms.

Exploring the role of oral microbiome dysbiosis in cardiometabolic syndrome and smoking.

Oral microbiome research has gained significant interest in recent years due to its potential impact on overall health. Smoking has been identified as a significant modulator of the oral microbiome composition, leading to dysbiosis and possible health consequences. Research has primarily focused on the association between smoking and oral microbiome, as well as smoking's association with cardiometabolic syndrome (CMS). This narrative review presents an overview of the recent findings and current knowledge on the oral microbiome and its role in CMS, including the effects of smoking and ethnicity. We discussed the development and composition of the oral microbiome and the association of periodontitis with diabetes and cardiovascular diseases. Furthermore, we highlighted the correlations between oral microbiome and CMS factors, such as diabetes, hypertension, dyslipidemia, and obesity. There is a need for further research in this area to better understand the mechanisms underlying the impact of smoking on oral microbiome dysbiosis and the development of CMS. Interestingly, geographic location and ethnicity have been shown to impact the oral microbiome profiles across populations. This knowledge will help develop personalized disease prevention and treatment approaches considering individual differences in oral microbiome composition. Understanding the complex interplay between oral microbiome, smoking, and CMS is essential for developing effective prevention and treatment strategies for a wide range of diseases.

Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.

Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota's contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.

A distinctive subgingival microbiome in patients with periodontitis and Alzheimer's disease compared with cognitively unimpaired periodontitis patients.

AIM: Periodontitis is caused by dysbiosis of oral microbes and is associated with increased cognitive decline in Alzheimer's disease (AD), and recently, a potential functional link was proposed between oral microbes and AD. We compared the oral microbiomes of patients with or without AD to evaluate the association between oral microbes and AD in periodontitis. MATERIALS AND METHODS: Periodontitis patients with AD (n = 15) and cognitively unimpaired periodontitis patients (CU) (n = 14) were recruited for this study. Each patient underwent an oral examination and neuropsychological evaluation. Buccal, supragingival and subgingival plaque samples were collected, and microbiomes were analysed by next-generation sequencing. Alpha diversity, beta diversity, linear discriminant analysis effect size, analysis of variance-like differential expression analysis and network analysis were used to compare group oral microbiomes. RESULTS: All 29 participants had moderate to severe periodontitis. Group buccal and supragingival samples were indistinguishable, but subgingival samples demonstrated significant alpha and beta diversity differences. Differential analysis showed subgingival samples of the AD group had higher prevalence of Atopobium rimae, Dialister pneumosintes, Olsenella sp. HMT 807, Saccharibacteria (TM7) sp. HMT 348 and several species of Prevotella than the CU group. Furthermore, subgingival microbiome network analysis revealed a distinct, closely connected network in the AD group comprised of various Prevotella spp. and several anaerobic bacteria. CONCLUSIONS: A unique microbial composition was discovered in the subgingival region in the AD group. Specifically, potential periodontal pathogens were found to be more prevalent in the subgingival plaque samples of the AD group. These bacteria may possess a potential to worsen periodontitis and other systemic diseases. We recommend that AD patients receive regular, careful dental check-ups to ensure proper oral hygiene management.

Association of Oral Microbiome Diversity and All-Cause Mortality in the General US Population and in Individuals With Chronic Diseases: A Prospective Cohort Study.

AIM: To investigate whether oral microbiome diversity is associated with all-cause mortality in the general US population and in individuals with chronic diseases. MATERIALS AND METHODS: We included 8224 individuals with oral microbiome diversity data from the National Health and Nutrition Examination Survey (2009-2012), representing 164,000,205 US adults, using a survey-weighted analysis method. Cox regression analyses were performed to identify the association between oral microbiome diversity and all-cause mortality. RESULTS: During a survey-weighted mean follow-up period of 8.86 years, 429 all-cause deaths (survey-weighted number: 7,124,920) occurred in 8224 participants. Cox regression analysis revealed that higher oral microbiome diversity was significantly associated with a lower all-cause mortality risk. Significant differences in all-cause mortality risk were observed among the different clusters based on oral microbiome ß-diversity (log-rank p < 0.001). Subgroup analyses revealed that the oral microbiome diversity was independently associated with all-cause mortality in individuals with diabetes mellitus and hypertension. A multivariate logistic regression model showed that current smoking and antibiotic use were significantly associated with lower oral microbiome α diversity. CONCLUSIONS: Higher oral microbiome diversity was significantly associated with a lower all-cause mortality risk in the general US population and in individuals with diabetes mellitus and hypertension.