Melbourne Dental School - Research Publications
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ItemBreastmilk influences development and composition of the oral microbiome(TAYLOR & FRANCIS LTD, 2022-12-31)BACKGROUND: Human microbiomes assemble in an ordered, reproducible manner yet there is limited information about early colonisation and development of bacterial communities that constitute the oral microbiome. AIM: The aim of this study was to determine the effect of exposure to breastmilk on assembly of the infant oral microbiome during the first 20 months of life. METHODS: The oral microbiomes of 39 infants, 13 who were never breastfed and 26 who were breastfed for more than 10 months, from the longitudinal VicGeneration birth cohort study, were determined at four ages. In total, 519 bacterial taxa were identified and quantified in saliva by sequencing the V4 region of the bacterial 16S rRNA genes. RESULTS: There were significant differences in the development of the oral microbiomes of never breastfed and breastfed infants. Bacterial diversity was significantly higher in never breastfed infants at 2 months, due largely to an increased abundance of Veillonella and species from the Bacteroidetes phylum compared with breastfed infants. CONCLUSION: These differences likely reflect breastmilk playing a prebiotic role in selection of early-colonising, health-associated oral bacteria, such as the Streptococcus mitis group. The microbiomes of both groups became more heterogenous following the introduction of solid foods.
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ItemThe Microbiome in Pancreatic Cancer-Implications for Diagnosis and Precision Bacteriophage Therapy for This Low Survival Disease.(Frontiers Media SA, 2022)While the mortality rates for many cancers have decreased due to improved detection and treatments, that of pancreatic cancer remains stubbornly high. The microbiome is an important factor in the progression of many cancers. Greater understanding of the microbiome in pancreatic cancer patients, as well as its manipulation, may assist in diagnosis and treatment of this disease. In this report we reviewed studies that compared microbiome changes in pancreatic cancer patients and non-cancer patients. We then identified which bacterial genera were most increased in relative abundance across the oral, pancreatic, duodenal, and faecal tissue microbiomes. In light of these findings, we discuss the potential for utilising these bacteria as diagnostic biomarkers, as well as their potential control using precision targeting with bacteriophages, in instances where a causal oncogenic link is made.
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ItemTemporal development of the infant oral microbiome(TAYLOR & FRANCIS LTD, 2022-11-02)The human oral microbiome is becoming recognized as playing roles in health and disease well beyond the oral cavity over the lifetime of the individual. The oral microbiome is hypothesized to result from specific colonization events followed by a reproducible and ordered development of complex bacterial communities. Colonization events, proliferation, succession and subsequent community development are dependent on a range of host and environmental factors, most notably the neonate diet. It is now becoming apparent that early childhood and prenatal influences can have long term effects on the development of human oral microbiomes. In this review, the temporal development of the infant human oral microbiome is examined, with the effects of prenatal and postnatal influences and the roles of specific bacteria. Dietary and environmental factors, especially breastfeeding, have a significant influence on the development of the infant oral microbiome. The evidence available regarding the roles and functions of early colonizing bacteria is still limited, and gaps in knowledge where further research is needed to elucidate these specific roles in relation to health and disease still exist.
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ItemNo Preview AvailableStreptococcus salivarius K12 inhibits Candida albicans aggregation, biofilm formation and dimorphism(TAYLOR & FRANCIS LTD, 2021-08-09)Candida albicans causes candidiasis, particularly in immunocompromised patients. Streptococcus salivarius K12 (K12) is a probiotic isolated from a healthy oral cavity. The study aimed to determine the effect of K12 on C. albicans aggregation, biofilm formation and dimorphism. C. albicans ATCC MYA-4901, acquired immunodeficiency syndrome (AIDS) isolate (ALC2), and oral cancer isolate (ALC3) and K12 were used in the study. All C. albicans strains and K12 were grown in yeast peptone dextrose agar and brain heart infusion agar, respectively, prior to aggregation, biofilm and dimorphism assays. Auto-aggregation of C. albicans MYA-4901 and ALC2 was categorised as high, while the co-aggregation of the strains was low in the presence of K12. C. albicans total cell count decreased significantly when co-cultured with K12 compared with monocultured C. albicans biofilm (p < 0.05). Inhibition of yeast-to-hyphae transition was also observed when co-cultured with K12. In conclusion, K12 inhibits C. albicans aggregation, biofilm formation and dimorphism.
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ItemMicrobiome profiles of non-responding and responding paired periodontitis sites within the same participants following non-surgical treatment(TAYLOR & FRANCIS LTD, 2022-12-31)AIM: Periodontitis is a site-specific, chronic disease treated by non-surgical debridement of subgingival plaque. We aimed to determine the microbiome of sites that did not respond to this treatment (NR) compared with paired good responding (GR) sites before and after treatment. MATERIALS AND METHODS: In a longitudinal cohort study, clinical parameters of disease and biological samples were taken prior to and 3 months after treatment. Twelve NR sites from six participants were paired with GR sites within the same participant. Subgingival plaque samples were subjected to bacterial community analysis using 16S rRNA gene sequencing. RESULTS: There were no significant differences in clinical parameters and microbial communities at baseline between GR and NR sites. Bacterial communities in deep pockets were dominated by a small number of species, notably Porphyromonas gingivalis and Treponema denticola. In NR sites three months after treatment there was no significant change in bacterial composition whilst there was a collapse in the abundance of pathobionts in GR sites. CONCLUSION: NR sites were not identifiable prior to treatment by clinical or microbiological parameters. Treatment failed to disrupt pathogenic bacterial community in NR sites. Targeted suppression of particular species should be considered to initiate community collapse and aid disease resolution.
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ItemOral Antibiotic for Empirical Management of Acute Dentoalveolar Infections-A Systematic Review(MDPI, 2021-03)Concerns regarding increasing antibiotic resistance raise the question of the most appropriate oral antibiotic for empirical therapy in dentistry. The aim of this systematic review was to investigate the antibiotic choices and regimens used to manage acute dentoalveolar infections and their clinical outcomes. A systematic review was undertaken across three databases. Two authors independently screened and quality-assessed the included studies and extracted the antibiotic regimens used and the clinical outcomes. Searches identified 2994 studies, and after screening and quality assessment, 8 studies were included. In addition to incision and drainage, the antibiotics used to manage dentoalveolar infections included amoxicillin, amoxicillin/clavulanic acid, cefalexin, clindamycin, erythromycin, metronidazole, moxifloxacin, ornidazole and phenoxymethylpenicillin. Regimens varied in dose, frequency and duration. The vast majority of regimens showed clinical success. One study showed that patients who did not receive any antibiotics had the same clinical outcomes as patients who received broad-spectrum antibiotics. The ideal choice, regimen and spectrum of empirical oral antibiotics as adjunctive management of acute dentoalveolar infections are unclear. Given that all regimens showed clinical success, broad-spectrum antibiotics as first-line empirical therapy are unnecessary. Narrow-spectrum agents appear to be as effective in an otherwise healthy individual. This review highlights the effectiveness of dental treatment to address the source of infection as being the primary factor in the successful management of dentoalveolar abscesses. Furthermore, the role of antibiotics is questioned in primary space odontogenic infections, if drainage can be established.
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ItemBugs and Brains, the Gut and Mental Health Study: a mixed-methods study investigating microbiota composition and function in anxiety, depression and irritable bowel syndrome(BMJ PUBLISHING GROUP, 2021)INTRODUCTION: Research has highlighted relationships between the micro-organisms that inhabit our gastrointestinal tract (oral and gut microbiota) with host mood and gastrointestinal functioning. Mental health disorders and functional gastrointestinal disorders co-occur at high rates, although the mechanisms underlying these associations remain unclear. The Bugs and Brains Study aims to investigate complex relationships between anxiety/depression and irritable bowel syndrome (IBS) in two ways. First, its primary component will compare the gut and oral microbiota in females with anxiety/depression and/or IBS relative to controls, and investigate underlying physiological, endocrine and immune factors, as well as associations with diet and psychosocial factors. In an ancillary component, the study will also investigate gastrointestinal and mental health symptoms in a larger sample, and explore relationships with diet, exercise, oral health, substance use, medical history, early life adversity and psychosocial factors. METHODS AND ANALYSIS: The Bugs and Brains Study aims to recruit 160 females to the primary component: (1) 40 controls; (2) 40 participants with a depressive/anxiety disorder, but no IBS; (3) 40 participants with IBS, but no depressive/anxiety disorder and (4) 40 participants with both depressive/anxiety disorder and IBS. Participation is completed within 1 month, and involves comprehensive questionnaires, anthropometrics, a diagnostic clinical interview, collection of two saliva samples, and stool, urine and hair samples. This study aims to use a systems biology approach to characterise oral and gut microbial composition and function using 16S rRNA gene sequencing and nuclear MR spectroscopy. As part of the ancillary component, it will collect questionnaire data from 1000 participants aged 18-40 years, capturing mental health, gastrointestinal health, oral health, diet and psychosocial factors. ETHICS AND DISSEMINATION: Approval was granted by the University of Melbourne Human Research Ethics Committee (#1749221). All participants voluntarily provided informed consent. Results will be published in peer-reviewed journals and presented at scientific conferences.
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ItemNo Preview AvailableNutrition and oral health in early childhood: associations with formal and informal childcare(CAMBRIDGE UNIV PRESS, 2021-04)OBJECTIVE: To examine associations between childcare type and nutrition and oral health indicators. DESIGN: Cross-sectional data extracted from a longitudinal birth cohort. Parent-completed FFQ and questions regarding oral health and childcare use. The associations between childcare type, classified into four groups: parent care only (PCO), formal childcare only (FCO), informal childcare only (ICO) or combination of care (F&I), and nutrition and oral health indicators were examined. SETTING: Home and childcare. PARTICIPANTS: Families with children aged 3 years (n 273) and 4 years (n 249) in Victoria, Australia. RESULTS: No associations were observed between childcare type and core food/beverage consumption or oral health indicators. For discretionary beverages, compared with children receiving PCO at age 3 years, children in FCO or F&I were less likely to frequently consume fruit juice/drinks (FCO: adjusted OR (AOR) 0·41, 95 % CI 0·17, 0·96, P = 0·04; F&I: AOR 0·32, 95 % CI 0·14, 0·74, P = 0·008). At age 4 years, children receiving FCO or ICO were less likely to consume sweet beverages frequently compared with children receiving PCO: fruit juice/drink (ICO: AOR 0·42, 95 % CI 0·19, 0·94, P = 0·03; FCO: AOR 0·35, 95 % CI 0·14, 0·88, P = 0·03) and soft drink (ICO: AOR 0·23, 95 % CI 0·07, 0·74, P = 0·01; FCO: AOR 0·14, 95 % CI 0·03, 0·76, P = 0·02). CONCLUSIONS: Associations between childcare type and discretionary beverage intake were observed. Investigation into knowledge, attitudes and activities in formal and informal childcare settings is required to explore different health promotion practices that may influence nutrition and oral health.
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ItemNo Preview AvailableThe role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis(WILEY, 2020-10)Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin, has been reported as an essential molecule in epithelial damage and host recognition of C albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C albicans such as adhesion, biofilm formation and filamentation properties. This review discusses the recent epidemiological burden of oral cancer and highlights the significance of the ECE1 gene and the ECE1 protein breakdown product, candidalysin in oral malignancy. The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.
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ItemMetabolic cooperativity betweenPorphyromonas gingivalisandTreponema denticola(TAYLOR & FRANCIS LTD, 2020-01-01)BACKGROUND: Porphyromonas gingivalis and Treponema denticola are proteolytic periodontopathogens that co-localize in polymicrobial subgingival plaque biofilms, display in vitro growth symbiosis and synergistic virulence in animal models of disease. These symbioses are underpinned by a range of metabolic interactions including cooperative hydrolysis of glycine-containing peptides to produce free glycine, which T. denticola uses as a major energy and carbon source. OBJECTIVE: To characterize the P. gingivalis gene products essential for these interactions. Methods: The P. gingivalis transcriptome exposed to cell-free T. denticola conditioned medium was determined using RNA-seq. P. gingivalis proteases potentially involved in hydrolysis of glycine-containing peptides were identified using a bioinformatics approach. RESULTS: One hundred and thirty-twogenes displayed differential expression, with the pattern of gene expression consistent with succinate cross-feeding from T. denticola to P. gingivalis and metabolic shifts in the P. gingivalis folate-mediated one carbon superpathway. Interestingly, no P. gingivalis proteases were significantly up-regulated. Three P. gingivalis proteases were identified as candidates and inactivated to determine their role in the release of free glycine. P. gingivalis PG0753 and PG1788 but not PG1605 are involved in the hydrolysis of glycine-containing peptides, making free glycine available for T. denticola utilization. CONCLUSION: Collectively these metabolic interactions help to partition resources and engage synergistic interactions between these two species.