Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention.

PURPOSE: Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients. EXPERIMENTAL DESIGN: We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n = 10, mean age: 10.7 ± 6.6 years) and after a 6-month oral hygiene intervention (n = 9,mean age: 11.6 ± 5.27 years), and from 12 healthy controls. RESULTS: We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins. CONCLUSIONS AND CLINICAL RELEVANCE: SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.

Microbial diagnostics in periodontal diseases.

Microbial analytical methods have been instrumental in elucidating the complex microbial etiology of periodontal diseases, by shaping our understanding of subgingival community dynamics. Certain pathobionts can orchestrate the establishment of dysbiotic communities that can subvert the host immune system, triggering inflammation and tissue destruction. Yet, diagnosis and management of periodontal conditions still rely on clinical and radiographic examinations, overlooking the well-established microbial etiology. This review summarizes the chronological emergence of periodontal etiological models and the co-evolution with technological advances in microbial detection. We additionally review the microbial analytical approaches currently accessible to clinicians, highlighting their value in broadening the periodontal assessment. The epidemiological importance of obtaining culture-based antimicrobial susceptibility profiles of periodontal taxa for antibiotic resistance surveillance is also underscored, together with clinically relevant analytical approaches to guide antibiotherapy choices, when necessary. Furthermore, the importance of 16S-based community and shotgun metagenomic profiling is discussed in outlining dysbiotic microbial signatures. Because dysbiosis precedes periodontal damage, biomarker identification offers early diagnostic possibilities to forestall disease relapses during maintenance. Altogether, this review highlights the underutilized potential of clinical microbiology in periodontology, spotlighting the clinical areas most conductive to its diagnostic implementation for enhancing prevention, treatment predictability, and addressing global antibiotic resistance.

Systemic antibiotics in the surgical treatment of peri-implantitis: A randomized placebo-controlled trial.

AIM: To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. MATERIALS AND METHODS: Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. RESULTS: A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. CONCLUSIONS: Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

Bacterial symbionts in oral niche use type VI secretion nanomachinery for fitness increase against pathobionts.

Microbial ecosystems experience spatial and nutrient restrictions leading to the coevolution of cooperation and competition among cohabiting species. To increase their fitness for survival, bacteria exploit machinery to antagonizing rival species upon close contact. As such, the bacterial type VI secretion system (T6SS) nanomachinery, typically expressed by pathobionts, can transport proteins directly into eukaryotic or prokaryotic cells, consequently killing cohabiting competitors. Here, we demonstrate for the first time that oral symbiont Aggregatibacter aphrophilus possesses a T6SS and can eliminate its close relative oral pathobiont Aggregatibacter actinomycetemcomitans using its T6SS. These findings bring nearer the anti-bacterial prospects of symbionts against cohabiting pathobionts while introducing the presence of an active T6SS in the oral cavity.

Bacteriome and mycobiome dysbiosis in oral mucosal dysplasia and oral cancer.

It has long been considered that the oral microbiome is tightly connected to oral health and that dysbiotic changes can be detrimental to the occurrence and progression of dysplastic oral mucosal lesions or oral cancer. Improved understanding of the concepts of microbial dysbiosis together with advances in high-throughput molecular sequencing of these pathologies have charted in greater microbiological detail the nature of their clinical state. This review discusses the bacteriome and mycobiome associated with oral mucosal lesions, oral candidiasis, and oral squamous cell carcinoma, aiming to delineate the information available to date in pursuit of advancing diagnostic and prognostic utilities for oral medicine.

Air powder waterjet technology using erythritol or glycine powders in periodontal or peri-implant prophylaxis and therapy: A consensus report of an expert meeting.

OBJECTIVES: To attain a collective expert opinion on the use of air powder waterjet technology (APWT) with erythritol and glycine powders in the prophylaxis and therapy of periodontal and peri-implant diseases. MATERIAL AND METHODS: In the first step, a modified one-round online Delphi survey including 44 five-point Likert scale questions was conducted among a group of 10 expert clinicians and researchers with thorough knowledge and experience in this topic. In the second step, the single questions and the survey results were discussed during a meeting, and consensus statements were formulated, respectively. RESULTS: An agreement was reached on most items, especially opinions supporting glycine and erythritol powders as favorable with respect to efficiency, safety, and comfort. More scientific evidence is needed to support the improvement in clinical attachment on teeth and implants, especially when APWT with erythritol is used. In addition, APWT needs more long-term evaluation and studies in terms of microbiome/microbiological effects as well as effects on the inflammatory response on natural teeth and implants, also in light of a guided biofilm therapy concept. CONCLUSIONS: In line with the expert opinions and supported by the evidence, it was concluded that the use of APWT with erythritol and glycine powders in nonsurgical periodontal and peri-implant therapy and prophylaxis is patient compliant and efficient.

A Mapping Review of the Pathogenesis of Peri-Implantitis: The Biofilm-Mediated Inflammation and Bone Dysregulation (BIND) Hypothesis.

This mapping review highlights the need for a new paradigm in the understanding of peri-implantitis pathogenesis. The biofilm-mediated inflammation and bone dysregulation (BIND) hypothesis is proposed, focusing on the relationship between biofilm, inflammation, and bone biology. The close interactions between immune and bone cells are discussed, with multiple stable states likely existing between clinically observable definitions of peri-implant health and peri-implantitis. The framework presented aims to explain the transition from health to disease as a staged and incremental process, where multiple factors contribute to distinct steps towards a tipping point where disease is manifested clinically. These steps might be reached in different ways in different patients and may constitute highly individualised paths. Notably, factors affecting the underlying biology are identified in the pathogenesis of peri-implantitis, highlighting that disruptions to the host-microbe homeostasis at the implant-mucosa interface may not be the sole factor. An improved understanding of disease pathogenesis will allow for intervention on multiple levels and a personalised treatment approach. Further research areas are identified, such as the use of novel biomarkers to detect changes in macrophage polarisation and activation status, and bone turnover.

Profiling Antibiotic Susceptibility among Distinct Enterococcus faecalis Isolates from Dental Root Canals.

Enterococcus faecalis, a leading multi-resistant nosocomial pathogen, is also the most frequently retrieved species from persistently infected dental root canals, suggesting that the oral cavity is a possible reservoir for resistant strains. However, antimicrobial susceptibility testing (AST) for oral enterococci remains scarce. Here, we examined the AST profiles of 37 E. faecalis strains, including thirty-four endodontic isolates, two vanA-type vancomycin-resistant isolates, and the reference strain ATCC-29212. Using Etest gradient strips and established EUCAST standards, we determined minimum inhibitory concentrations (MICs) for amoxicillin, vancomycin, clindamycin, tigecycline, linezolid, and daptomycin. Results revealed that most endodontic isolates were susceptible to amoxicillin and vancomycin, with varying levels of intrinsic resistance to clindamycin. Isolates exceeding the clindamycin MIC of the ATCC-29212 strain were further tested against last-resort antibiotics, with 7/27 exhibiting MICs matching the susceptibility breakpoint for tigecycline, and 1/27 reaching that of linezolid. Both vanA isolates confirmed vancomycin resistance and demonstrated resistance to tigecycline. In conclusion, while most endodontic isolates remained susceptible to first-line antibiotics, several displayed marked intrinsic clindamycin resistance, and MICs matched tigecycline's breakpoint. The discovery of tigecycline resistance in vanA isolates highlights the propensity of clinical clone clusters to acquire multidrug resistance. Our results emphasize the importance of implementing AST strategies in dental practices for continued resistance surveillance.