Oral microbes and the formation of cerebral abscesses: A single-centre retrospective study.

OBJECTIVE: Intracranial abscesses are relatively uncommon, but can result in significant mortality and morbidity. Whilst many potential causes of brain abscesses are recognised, in many cases the origin of infection remains clinically unidentified. Our objective was to investigate the role of bacteria found in the oral cavity in the development of brain abscesses. METHODS: A retrospective analysis was performed using data from 87 patients admitted to a single UK neurosurgical unit with brain abscesses over a 16-year period. Using microbiological data obtained from abscess sampling and peripheral cultures, species of bacteria were categorised in patients where no primary source of infection was identified (NSI) for their brain abscess (n = 52), or where an infective source (ISI) was identified. The microbiological data was then screened to identify common oral bacteria in each group. RESULTS: Brain abscesses from the ISI group (n = 35) demonstrated a significantly lower preponderance of oral bacteria (n = 8), than the NSI group (n = 29) (p < 0.05). Brain abscesses from the NSI group also had significantly higher counts of Streptococcus anginosus compared to ISI (p < 0.05), with brain abscesses being most common in the frontal and parietal lobes for both ISI and NSI. CONCLUSIONS: These findings suggest that the oral cavity could be considered as a source of occult infection in cases of brain abscess where no clear cause has been identified. Future studies should include oral screening and microbiome analysis to better understand the mechanisms involved and develop approaches for prevention. CLINICAL SIGNIFICANCE STATEMENT: Oral bacteria may be an under-recognised cause of brain abscesses. Careful review of oral health in brain abscess patients may help establish causation, particularly in patients with no cause for their abscess identified. Good levels of oral health may help prevent the development of brain abscesses in some individuals.

Effects of chlorhexidine mouthwash on the oral microbiome.

INTRODUCTION/OBJECTIVES: Chlorhexidine (CHX) is a commonly used mouthwash with potent anti-microbial effects useful for the management of oral disease. However, we are moving away from the view of simply 'killing' bacteria, towards managing oral microbial ecosystems (oral microbiome), as an integrated system, to promote oral and systemic health. Here, we aimed to review the effects of CHX mouthwash on the balance of microbial communities in the mouth in vivo in oral health and disease. SOURCES AND STUDY SECTION: The hierarchy of evidence was applied, with systematic reviews and randomised controlled trials consulted where available and case controlled studies being described thereafter. Search terms for each subject category were entered into MEDLINE, PubMed, Google Scholar and the Cochrane database. Focussing on metagenomics studies provides unique overview of the oral microbiome as an integrated system. DATA: Evidence was limited, but several next generation sequencing case-controlled studies suggested that in an integrated system, CHX may cause a shift towards lower bacterial diversity and abundance, in particular nitrate-reducing bacteria in vivo. CHX also appeared to alter salivary pH, lactate, nitrate and nitrite concentrations in saliva. Evidence regarding the effects of CHX on the oral microbiome during oral disease is still emerging. CONCLUSIONS: CHX alters the composition the oral microbiome. However, as CHX use remains widespread in dentistry to manage oral disease, urgent research using metagenomics studies of microbial communities in vivo are still needed to determine CHX mouthwash is 'good', 'bad' or otherwise for bacteria, in the context of oral and systemic health.

Current uses of chlorhexidine for management of oral disease: a narrative review.

OBJECTIVES: Chlorhexidine (CHX) is a commonly used antiseptic mouthwash, used by dental practitioners and the public, due to its antimicrobial effects. The aim of this article was to provide a narrative review of current antimicrobial uses of CHX relevant to dentistry in the context of oral diseases, highlighting need for further studies to support its safe and appropriate use. STUDY SELECTION, DATA AND SOURCES: Randomised controlled trials, systematic reviews and national (UK and US) guidelines were consulted where available, with search terms for each subject category entered into MEDLINE, PubMed, Google Scholar and the Cochrane database. RESULTS: Some evidence existed to support adjunctive short-term use of CHX to manage dental plaque, and reduce clinical symptoms of gingivitis, dry socket, as well as reduce aerosolisation of bacteria. However, use must be weighed alongside the less desirable effects of CHX, including extrinsic staining of teeth, antimicrobial resistance to antiseptic agents and the rare, but fatal, allergic reactions to CHX. Conversely, evidence for the effectiveness of chlorhexidine to manage or prevent periodontitis, dental caries, necrotising periodontal diseases, peri-implantitis, and infections associated with extraction and aerosolised viruses remains less certain. CONCLUSIONS: The use of CHX in dentistry and oral healthcare continues to be widespread and thus it is important that dental practitioners understand that, based on its differential mechanisms of action on different microbes, appropriate clinical and dental use of CHX should be oral disease specific. However, further scientific and clinical research is required before full recommendations can be made.

Comparative analysis of total salivary lipopolysaccharide chemical and biological properties with periodontal status.

OBJECTIVE: Clinical manifestations of Gram-negative bacteria mediated diseases can be influenced by how the host senses their major microbe-associated molecular pattern, the cell wall lipopolysaccharide (LPS). Keystone periodontal pathogens can produce a heterogeneous population of LPS molecules, with strikingly different host-microbiome interactions and immune outcomes. DESIGN: Structure-function correlations of salivary LPS extracts in patients with periodontitis before and after periodontal treatment and healthy volunteers were analysed by comparing its lipid A and carbohydrate chain chemical structure and evaluating its endotoxin activity and inflammatory potential. RESULTS: Salivary LPS extracts from periodontitis patients were characterised by high m/z lipid A mass-spectrometry peaks, corresponding to over-acylated and phosphorylated lipid A ions and by a combination of rough and smooth LPS carbohydrate moieties. In contrast, gingival health was defined by the predominance of low m/z lipid A peaks, consistent with under-acylated and hypo-phosphorylated lipid A molecular signatures, with long and intermediate carbohydrate chains as determined by silver staining. Total, diseased salivary LPS extracts were stronger inducers of the recombinant factor C assay and triggered significantly higher levels of TNF-α, IL-8 and IP-10 production in THP-1 cells, compared to almost immunosilent healthy samples. Interestingly, salivary LPS architecture, endotoxin activity, and inflammatory potential were well conserved after periodontal therapy and showed similarities to diseased samples. CONCLUSIONS: This study sheds new light on molecular pathogenic mechanisms of oral dysbiotic communities and indicates that the regulation of LPS chemical structure is an important mechanism that drives oral bacteria-host immune system interactions into either a symbiotic or pathogenic relationship.

Subgingival lipid A profile and endotoxin activity in periodontal health and disease.

OBJECTIVES: Regulation of lipopolysaccharide (LPS) chemical composition, particularly its lipid A domain, is an important, naturally occurring mechanism that drives bacteria-host immune system interactions into either a symbiotic or pathogenic relationship. Members of the subgingival oral microbiota can critically modulate host immuno-inflammatory responses by synthesizing different LPS isoforms. The objectives of this study were to analyze subgingival lipid A profiles and endotoxin activities in periodontal health and disease and to evaluate the use of the recombinant factor C assay as a new, lipid A-based biosensor for personalized, point-of-care periodontal therapy. MATERIALS AND METHODS: Subgingival plaque samples were collected from healthy individuals and chronic periodontitis patients before and after periodontal therapy. Chemical composition of subgingival lipid A moieties was determined by ESI-Mass Spectrometry. Endotoxin activity of subgingival LPS extracts was assessed using the recombinant factor C assay, and their inflammatory potential was examined in THP-1-derived macrophages by measuring TNF-α and IL-8 production. RESULTS: Characteristic lipid A molecular signatures, corresponding to over-acylated, bi-phosphorylated lipid A isoforms, were observed in diseased samples. Healthy and post-treatment samples were characterized by lower m/z peaks, related to under-acylated, hypo-phosphorylated lipid A structures. Endotoxin activity levels and inflammatory potentials of subgingival LPS extracts from periodontitis patients were significantly higher compared to healthy and post-treatment samples. CONCLUSIONS: This is the first study to consider structure-function-clinical implications of different lipid A isoforms present in the subgingival niche and sheds new light on molecular pathogenic mechanisms of subgingival biofilm communities. CLINICAL RELEVANCE: Subgingival endotoxin activity (determined by lipid A chemical composition) could be a reliable, bacterially derived biomarker and a risk assessment tool for personalized periodontal care.

Exposure to Porphyromonas gingivalis LPS during macrophage polarisation leads to diminished inflammatory cytokine production.

OBJECTIVE: The objective of the present study was to determine the effects of concurrent LPS and cytokine priming, reflective of the in vivo milieu, on macrophage production of key periodontitis associated cytokines TNF, IL-1ß and IL-6. DESIGN: THP-1 cells were pre-treated with combinations of Porphyromonas gingivalis and Escherichia coli lipopolysaccharide (LPS), concurrently with polarising cytokines IFNγ and IL-4, or PMA as a non-polarised control. Production of key periodontitis associated cytokines in response to subsequent LPS challenge were measured by enzyme - linked immunosorbent assay. RESULTS: Compared with cells incubated with IFNγ or IL-4 alone in the "polarisation" phase, macrophages that were incubated with LPS during the first 24h displayed a down-regulation of TNF and IL-1ß production upon secondary LPS treatment in the "activation" phase. In all three macrophage populations (M0, M1 and M2), pre-treatment with P. gingivalis LPS during the polarisation process led to a significant decrease in TNF production in response to subsequent activation by LPS (p=0.007, p=0.002 and p=0.004, respectively). Pre-treatment with E. coli LPS also led to a significant down-regulation in TNF production in all three macrophage populations (p<0.001). Furthermore, the presence of E. coli LPS during polarisation also led to the down-regulation of IL-1ß in the M1 population (p<0.001), whereas there was no measurable effect on IL-1ß production in M0 or M2 macrophages. There was no significant effect on IL-6 production. CONCLUSIONS: Macrophages become refractory to further LPS challenge, whereby production of key periodontitis associated cytokines TNF and IL-1ß is reduced after exposure to LPS during the polarisation phase, even in the presence of inflammatory polarising cytokines. This diminished cytokine response may lead to the reduced ability to clear infection and transition to chronic inflammation seen in periodontitis.