Successful endodontic treatment reduces serum levels of cardiovascular disease risk biomarkers-high-sensitivity C-reactive protein, asymmetric dimethylarginine, and matrix metalloprotease-2.

AIM: To investigate serum biomarkers of inflammation 2 years following non-surgical root canal re-treatment (Re-RCT) and peri-apical surgery (PS). The results were correlated with signs and symptoms, treatment outcome, metabolic syndrome factors, infection with severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (COVID-19) infection and COVID-19 vaccination. METHODOLOGY: Subjects from our previous study were recalled for 2 years post-treatment follow-up. Changes to the patient's history (medical, dental, social) were noted. Periapical health of the treated teeth was examined both clinically and radiographically. Blood pressure, fasting HbA1C and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and total cholesterol (TC) levels were measured. Serum inflammatory marker levels were assayed using a Bio-Rad Bio-Plex 200 analyser and values at different time points within the same group were compared using a Wilcoxon signed-rank test and differences between groups with a Mann-Whitney test. Linear associations were tested using Pearson's correlations. RESULTS: The recall percentage at 2 years was 56.9% (n = 37), with a 100% radiographic success rate using periapical radiographs. In total, 21 cases (56.8%) were completely healed, and 16 cases (43.2%) were healing. Higher matrix metalloprotease 2 (MMP2) levels were present in the healing group compared to the healed group. Serum levels of high-sensitivity C-reactive protein (hs-CRP), asymmetric dimethylarginine (ADMA) and MMP-2 were significantly reduced (p ≤ .001) whereas other biomarkers showed significant increases at 2 year compared to pre-operative levels, while FGF-23 and ICAM-1 were not significantly increased. HbA1C (p = .015), TC (p = .003), LDL (p = .003) and HDL (p = .003) reduced significantly at 2 years post-treatment compared to their preoperative levels. COVID infection showed a significant association with MMP-9 (p = .048). CONCLUSIONS: hs-CRP, ADMA and MMP-2 can be regarded as prognostic biomarkers of successful Re-RCT and PS as they reduced at 2 year recall in cases which showed evidence of clinical and radiographic success. The successful treatment of chronic apical periodontitis is correlated with improvements in metabolic syndrome indicators, better glycemic control, and reduction at 2 year of some systemic inflammatory markers which are related to risks of cardiovascular disease events.

Biomarkers for diagnosis of stage III, grade C with molar incisor pattern periodontitis in children and young adults: a systematic review and meta-analysis.

AIM: To explore the existing salivary, gingival crevicular fluid (GCF), blood, and serum biomarkers associated with grade C molar-incisor pattern (C/MIP) periodontitis in systemically healthy children and young adults. MATERIALS AND METHODS: Cross-sectional, case-control, and cohort studies on stage III grade C periodontitis or former equivalent diagnosis with analysis of molecular biomarkers in saliva, GCF, blood, or serum were retrieved from six databases and screened based on the eligibility criteria. The risk of bias in included studies was evaluated. Meta-analysis was planned for biomarkers assessed using the same detection methods and sample type in at least two papers. RESULTS: Out of 5621 studies identified at initial screening, 28 papers were included in the qualitative analysis of which 2 were eligible for meta-analysis for IgG in serum samples. Eighty-seven biomarkers were assessed with the majority being higher in cases than in controls. Only the meta-analysis of total serum IgG with low heterogeneity value revealed a significant increase in its levels in C/MIPs compared to controls (standardised mean difference: 1.08; 95% CI: 0.76, 1.40). CONCLUSION: There is a paucity of data on biomarkers associated with molar-incisor pattern periodontitis. Although serum IgG levels are raised, other more specific biomarkers in saliva, GCF, and blood/serum may be promising but require further investigation.

The key players of dysbiosis in Noma disease; A systematic review of etiological studies.

Noma is a rapidly progressing periodontal disease with up to 90% mortality in developing countries. Poor, immunocompromised and severely malnourished children (2 to 6 years old) are mostly affected by Noma. Prevention and effective management of Noma is hindered by the lack of sufficient cohesive studies on the microbial etiology of the disease. Research efforts have not provided a comprehensive unified story of the disease. Bridging the gap between existing studies gives an insight on the disease pathogenesis. This current systematic review of etiological studies focuses on the key players of dysbiosis in Noma disease. This review was performed in accordance with the Preferred Reporting Items for Systemic review and Meta-Analyses (PRISMA) statement. Web of Science, MEDLINE via PubMed, Cochrane Library, Scopus, and Science Direct were searched electronically for clinical trials which applied culture dependent or molecular techniques to identify oral microbiota from Noma patients. Trials which involved periodontal diseases except Noma were excluded. After screening 275 articles, 153 full-texts articles were assessed for eligibility of which eight full text articles were selected for data extraction and analysis. The results show that 308 samples from 169 Noma participants (6 months to 15 years old) have been used in clinical trials. There was some variance in the microbiome identified due to the use of 3 different types of samples (crevicular fluid, subgingival plaque, and swabbed pus) and the ambiguity of the stage or advancement of Noma in the studies. Other limitations of the studies included in this review were: the absence of age-matched controls in some studies; the constraints of colony morphology as a tool in distinguishing between virulent fusobacterium genus at the species level; the difficulty in culturing spirochaetes in the laboratory; the choice of primers in DNA amplification; and the selection of probe sets in gene sequencing. This systematic review highlights spirochaetes and P. intermedia as putative trigger organisms in Noma dysbiosis, shows that F. nucleatum promotes biofilms formation in late stages of the disease and suggests that future studies should be longitudinal, with high throughput genome sequencing techniques used with gingival plaque samples from early stages of Noma.

Alterations in the Oral Microbiome Associated With Diabetes, Overweight, and Dietary Components.

The Mediterranean diet (MedDiet) represents the traditional food consumption patterns of people living in countries bordering the Mediterranean Sea and is associated with a reduced incidence of obesity and type-2 diabetes mellitus (T2DM). The objective of this study was to examine differences in the composition of the oral microbiome in older adults with T2DM and/or high body mass index (BMI) and whether the microbiome was influenced by elements of a MedDiet. Using a nested case-control design individuals affected by T2DM were selected from the Seniors-ENRICA-2 cohort concurrently with non-diabetic controls. BMI was measured, a validated dietary history taken, and adherence to a Mediterranean diet calculated using the MEDAS (Mediterranean Diet Adherence Screener) index. Oral health status was assessed by questionnaire and unstimulated whole mouth saliva was collected, and salivary flow rate calculated. Richness and diversity of the salivary microbiome were reduced in participants with T2DM compared to those without diabetes. The bacterial community structure in saliva showed distinct "signatures" or "salivatypes," characterized by predominance of particular bacterial genera. Salivatype 1 was more represented in subjects with T2DM, whilst those with obesity (BMI ≥ 30 kg/m2) had a predominance of salivatype 2, and control participants without T2DM or obesity had an increased presence of salivatype 3. There was an association of salivatype 1 with increased consumption of sugary snacks combined with reduced consumption of fish/shellfish and nuts. It can be concluded that the microbial community structure of saliva is altered in T2DM and obesity and is associated with altered consumption of particular food items. In order to further substantiate these observations a prospective study should be undertaken to assess the impact of diets aimed at modifying diabetic status and reducing weight.

The impact of apical periodontitis, non-surgical root canal retreatment and periapical surgery on serum inflammatory biomarkers.

AIM: The aim of the study was to measure serum levels of molecular markers of inflammation in patients undergoing non-surgical root canal retreatment (Re-RCT) and periapical surgery (PS) for the treatment of apical periodontitis and to establish if such levels are influenced by the size of apical radiolucencies at baseline and by the treatment outcome. METHODOLOGY: A total of 115 participants were recruited (n = 50 Controls, n = 35 Re-RCT, n = 30 PS). Preoperative periapical radiographs and cone beam CT (CBCT) scans of teeth were taken. Blood was collected from treatment groups at baseline, 3-, 6-, and 12-month post-treatment and from controls at baseline and 12 months. Serum levels of IL-1ß, IL-6, IL-8, TNF-α, Pentraxin 3, ICAM-1, VCAM-1, hs-CRP, FGF-23, MMP-2, MMP-8, MMP-9, C3 and ADMA were analysed using multiplex immunoassay and enzyme-linked immunosorbent assay. Different time points within the same group were compared using Wilcoxon signed-rank test, and differences between groups were analysed using the Mann-Whitney test. Non-linear association between different factors was assessed using Spearman's correlation. RESULTS: Preoperative serum levels of FGF-23, IL-1ß, hs-CRP and ADMA were significantly higher in the diseased groups compared with controls (p < .001; p = .008; p < .001; p = .013, respectively). The preoperative size of the radiolucency was associated with increased levels of FGF-23, IL-1ß and IL-6. At 3-months following treatment, IL-1ß, IL-8, hs-CRP, C3, MMP-2 and MMP-9 levels increased compared with baseline in treatment groups. IL-1ß and IL-8 further increased at 6 months, whereas FGF-23, hs-CRP, C3, MMP2 and MMP-9 decreased. One-year post-treatment, FGF-23, pentraxin-3 and ADMA were significantly reduced below baseline levels. At the 1-year review, CBCT revealed that 25.9% of treated cases completely healed, while 63% were healing, and 11.1% failed. Treatment outcome was found to be influenced by preoperative levels of ADMA and IL-8 levels at 6 months. CONCLUSIONS: Both symptomatic and asymptomatic apical periodontitis (AP) can contribute to increased levels of molecular markers of inflammation. A further transient inflammatory markers rise after root canal retreatment and apical surgery were demonstrated. Successful endodontic treatment and periapical surgery result in a long-term reduction in inflammatory marker levels.

The Role of TRP Channels in Nicotinic Provoked Pain and Irritation from the Oral Cavity and Throat: Translating Animal Data to Humans.

Tobacco smoking-related diseases are estimated to kill more than 8 million people/year and most smokers are willing to stop smoking. The pharmacological approach to aid smoking cessation comprises nicotine replacement therapy (NRT) and inhibitors of the nicotinic acetylcholine receptor, which is activated by nicotine. Common side effects of oral NRT products include hiccoughs, gastrointestinal disturbances and, most notably, irritation, burning and pain in the mouth and throat, which are the most common reasons for premature discontinuation of NRT and termination of cessation efforts. Attempts to reduce the unwanted sensory side effects are warranted, and research discovering the most optimal masking procedures is urgently needed. This requires a firm mechanistic understanding of the neurobiology behind the activation of sensory nerves and their receptors by nicotine. The sensory nerves in the oral cavity and throat express the so-called transient receptor potential (TRP) channels, which are responsible for mediating the nicotine-evoked irritation, burning and pain sensations. Targeting the TRP channels is one way to modulate the unwanted sensory side effects. A variety of natural (Generally Recognized As Safe [GRAS]) compounds interact with the TRP channels, thus making them interesting candidates as safe additives to oral NRT products. The present narrative review will discuss (1) current evidence on how nicotine contributes to irritation, burning and pain in the oral cavity and throat, and (2) options to modulate these unwanted side-effects with the purpose of increasing adherence to NRT. Nicotine provokes irritation, burning and pain in the oral cavity and throat. Managing these side effects will ensure better compliance to oral NRT products and hence increase the success of smoking cessation. A specific class of sensory receptors (TRP channels) are involved in mediating nicotine's sensory side effects, making them to potential treatment targets. Many natural (Generally Recognized As Safe [GRAS]) compounds are potentially beneficial modulators of TRP channels.

Calcium phosphate nanoparticles for potential application as enamel remineralising agent tested on hydroxyapatite discs.

Calcium phosphate exhibits excellent biocompatibility, and with particle size in the nanoscale, calcium phosphate nanoparticles (CPNPs) were explored to replace the hydroxyapatite lost in the nanoporous teeth due to dental erosion. CPNPs (2% w/v) colloidally stabilised by sodium citrate were synthesised via co-precipitation. They were characterised in terms of particle size, morphology, crystallinity, Ca/P ratio and calcium ion release. To ensure uniformity of the substrate, hydroxyapatite (HA) discs were examined as an alternative substrate model to enamel. They were eroded in acetate buffer (0.5 M; pH 4.0) at various timepoints (1, 5, 10, 30 min, and 2, 4 h), and their physical differences compared to enamel were assessed in terms of surface microhardness, surface roughness and step height. The remineralisation properties of the synthesised CPNPs on eroded HA discs at different pH levels were investigated. It was established that CPNPs were heterogeneously deposited on the HA discs at pH 9.2, whereas newly precipitated minerals from CPNPs were potentially formed at pH 6.2.

Salivary Lactoferrin Expression in a Mouse Model of Alzheimer's Disease.

In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer's disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-ß (Aß) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion.

The salivary proteome reflects some traits of dietary habits in diabetic and non-diabetic older adults.

PURPOSE: Objective markers of usual diet are of interest as alternative or validating tools in nutritional epidemiology research. The main purpose of the work was to assess whether saliva protein composition can reflect dietary habits in older adults, and how type 2 diabetes impacted on the saliva-diet correlates. METHODS: 214 participants were selected from 2 European cohorts of community-dwelling older adults (3C-Bordeaux and Seniors-ENRICA-2), using a case-control design nested in each cohort. Cases were individuals with type 2 diabetes. Dietary information was obtained using the Mediterranean Diet Adherence Screener (MEDAS). Saliva was successfully obtained from 211 subjects, and its proteome analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: The relative abundance of 246 saliva proteins was obtained across all participants. The salivary proteome differed depending on the intake level of some food groups (especially vegetables, fruits, sweet snacks and red meat), in a diabetic status- and cohort-specific manner. Gene Set Enrichment Analysis suggested that some biological processes were consistently affected by diet across cohorts, for example enhanced platelet degranulation in high consumers of sweet snacks. Minimal models were then fitted to predict dietary variables by sociodemographic, clinical and salivary proteome variables. For the food group «sweet snacks¼, selected salivary proteins contributed to the predictive model and improved its performance in the Seniors-ENRICA-2 cohort and when both cohorts were combined. CONCLUSION: Saliva proteome composition of elderly individuals can reflect some aspects of dietary patterns.

Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson's disease.

Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement of the GI tract and enteric nervous system highlights the need for better understanding of the role of gut microbiota in GI complications in PD. Here, we investigate the gut microbiome of patients with PD using metagenomics and serum metabolomics. We integrate these data using metabolic modeling and construct an integrative correlation network giving insight into key microbial species linked with disease severity, GI dysfunction, and age of patients with PD. Functional analysis reveals an increased microbial capability to degrade mucin and host glycans in PD. Personalized community-level metabolic modeling reveals the microbial contribution to folate deficiency and hyperhomocysteinemia observed in patients with PD. The metabolic modeling approach could be applied to uncover gut microbial metabolic contributions to PD pathophysiology.

Comparing development and regeneration in the submandibular gland highlights distinct mechanisms.

A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Salivary gland duct ligation/deligation model was used as a regenerative model. Fgf10 and Sox9 expression changed during regeneration compared to homeostasis, suggesting that these key developmental genes play important roles during regeneration, however, significantly both displayed different patterns of expression in the regenerating gland compared to the developing gland. Regenerating glands, which during homeostasis had very few weakly expressing Sox9-positive cells in the striated/granular ducts, displayed elevated expression of Sox9 within these ducts. This pattern is in contrast to embryonic development, where Sox9 expression was absent in the proximally developing ducts. However, similar to the elevated expression at the distal tip of the epithelium in developing salivary glands, regenerating glands displayed elevated expression in a subpopulation of acinar cells, which during homeostasis expressed Sox9 at lower levels. A shift in expression of Fgf10 was observed from a widespread mesenchymal pattern during organogenesis to a more limited and predominantly epithelial pattern during homeostasis in the adult. This restricted expression in epithelial cells was maintained during regeneration, with no clear upregulation in the surrounding mesenchyme, as might be expected if regeneration recapitulated development. As both Fgf10 and Sox9 were upregulated in proximal ducts during regeneration, this suggests that the positive regulation of Sox9 by Fgf10, essential during development, is partially reawakened during regeneration using this model. Together these data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development.

Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands.

Little is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-ßgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.

Salivary changes in oxidative stress related to inflammation in oral and gastrointestinal diseases.

OBJECTIVES: The early diagnosis and monitoring of Crohn's disease (CD) and orofacial granulomatosis (OFG) might be facilitated by assaying potential disease biomarkers in saliva. Markers of oxidative stress and inflammation were assayed in salivas from patients with CD, OFG and concurrent OFG and CD (OFG + CD). SUBJECTS: Unstimulated whole mouth saliva was collected from 93 subjects, and immunoglobulin A (IgA), lactoferrin (LF) and myeloperoxidase (MPO) were determined by ELISA. Markers of oxidative stress and antioxidant status were assayed spectrophotometrically. RESULTS: Immunoglobulin A was significantly (p < .03) higher in experimental groups vs the control group. LF was significantly (p < .01) higher in OFG + CD compared to CTRL and CD. Ferric reducing antioxidant power was lower (p ≤ .009) in all experimental groups, and advanced glycation end products were higher (p ≤ .01) in CD and OFG + CD patients. CONCLUSION: Oxidative stress is increased in saliva in CD and OFG. Although MPO, a product of inflammatory cells, was not significantly increased, the other innate immune markers, IgA and LF, which are also secreted by salivary glands, were increased. This study suggests that saliva might be utilized in monitoring CD and OFG but further longitudinal studies focused on analysing a panel of salivary markers are needed.

Emerging nanomaterials for dental treatments.

The emergence of nanomaterials for dental treatments is encouraged by the nanotopography of the tooth structure, together with the promising benefits of nanomedicine. The use of nanoparticles in dentistry, also termed as 'nanodentistry', has manifested in applications for remineralisation, antimicrobial activity, local anaesthesia, anti-inflammation, osteoconductivity and stem cell differentiation. Besides the applications on dental tissues, nanoparticles have been used to enhance the mechanical properties of dental composites, improving their bonding and anchorage and reducing friction. The small particle size allows for enhanced permeation into deeper lesions, and reduction in porosities of dental composites for higher mechanical strength. The large surface area to volume ratio allows for enhanced bioactivity such as bonding and integration, and more intense action towards microorganisms. Controlled release of encapsulated bioactive molecules such as drugs and growth factors enables them to be delivered more precisely, with site-targeted delivery for localised treatments. These properties have benefitted across multiple fields within dentistry, including periodontology and endodontics and reengineering of dental prosthetics and braces. This review summarises the current literature on the emerging field of nanomaterials for dental treatments.

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals.

Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.

Systems Biology Approaches to Understand the Host-Microbiome Interactions in Neurodegenerative Diseases.

Neurodegenerative diseases (NDDs) comprise a broad range of progressive neurological disorders with multifactorial etiology contributing to disease pathophysiology. Evidence of the microbiome involvement in the gut-brain axis urges the interest in understanding metabolic interactions between the microbiota and host physiology in NDDs. Systems Biology offers a holistic integrative approach to study the interplay between the different biologic systems as part of a whole, and may elucidate the host-microbiome interactions in NDDs. We reviewed direct and indirect pathways through which the microbiota can modulate the bidirectional communication of the gut-brain axis, and explored the evidence of microbial dysbiosis in Alzheimer's and Parkinson's diseases. As the gut microbiota being strongly affected by diet, the potential approaches to targeting the human microbiota through diet for the stimulation of neuroprotective microbial-metabolites secretion were described. We explored the potential of Genome-scale metabolic models (GEMs) to infer microbe-microbe and host-microbe interactions and to identify the microbiome contribution to disease development or prevention. Finally, a systemic approach based on GEMs and 'omics integration, that would allow the design of sustainable personalized anti-inflammatory diets in NDDs prevention, through the modulation of gut microbiota was described.

The role of overweight in the association between the Mediterranean diet and the risk of type 2 diabetes mellitus: a mediation analysis among 21 585 UK biobank participants.

BACKGROUND: There is growing evidence that the Mediterranean (Medi) diet may lower the risk of type 2 diabetes mellitus (T2DM). Whether this association is due to the Medi diet by itself or is mediated by a diet-associated lower rate of overweight is uncertain. Our aim was to disentangle these relationships among UK adults. METHODS: Based on 21 585 participants from the UK Biobank cohort, the adherence to the Medi diet (high fruits, vegetables, legumes, cereals, fish, olive oil; low meat, dairy products; and intermediate alcohol intakes) was assessed (range 0-18). Data on diabetes were self-reported, and overweight was defined as a body mass index (BMI) ≥ 25 kg/m². A mediation analysis was implemented to disentangle the role of overweight in the Medi diet-T2DM relationship. RESULTS: The average baseline Medi diet score was 8.8 [standard deviation (SD) 2.6]. During a mean follow-up of 6.1 years, 473 individuals developed T2DM. A higher adherence to a Medi diet (+1 point) was associated with 14% decreased risk of T2DM [hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.82-0.90]. This association split into an indirect effect of 10%, mediated by lower odds of overweight (HR: 0.90, 95% CI: 0.87-0.92), and a direct effect of the Medi diet of 4% (HR: 0.96, 95% CI: 0.93-0.99), regardless of the effect mediated by overweight. CONCLUSIONS: Considered as a single mediator, reduced overweight mainly contributes to the association between greater Medi diet adherence and lower risk of T2DM on this British subsample. However, the direct effect of the diet on the risk of T2DM, even weaker, should not be overlooked.

Agonists of Orally Expressed TRP Channels Stimulate Salivary Secretion and Modify the Salivary Proteome.

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

Abundance and diversity of resistomes differ between healthy human oral cavities and gut.

The global threat of antimicrobial resistance has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the resistome, in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes. Here we analyse and compare the resistome profiles of 788 oral cavities worldwide with paired stool metagenomes. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. Within individuals, the highest abundances of antimicrobial resistance genes are found in the oral cavity, but the oral cavity contains a lower diversity of resistance genes compared to the gut. Additionally, co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

Reduced Salivary Mucin Binding and Glycosylation in Older Adults Influences Taste in an In Vitro Cell Model.

BACKGROUND: Taste loss is a significant problem in older adults, affecting quality of life and nutrition. Altered salivary rheology and loss of mucin function may contribute to taste loss by reducing mucosal defences in the oral cavity, impairing sensitivity to oral stimulants. This study aimed to investigate the effects of salivary rheology on taste loss in ageing. Salivary mucin glycosylation and binding to the oral epithelium was investigated in older and younger adults. A cell-based model was utilised to consider the role of saliva in taste loss. METHODS: Human subjects aged >60 years (n = 25) and 18-30 (n = 30) provided saliva samples which were analysed for viscosity, mucin composition and mucin binding to oral epithelial cells (TR146/MUC1). Oral epithelial cells (TR146/MUC1 and SCC090) provided models for taste receptor activation. RESULTS: Reduced levels and sialylation of MUC7 were evident in saliva of older adults which may lead to reduced viscoelasticity, while viscosity is unaffected. Impaired muco-adhesion of saliva from older adults was also observed. Saliva from older adults facilitated the bitter taste receptor activation less well than saliva from younger adults. The causes of taste dysfunction in older adults are unknown, but this study supports a role of saliva in facilitating the activation of taste receptors.