Primary supervisor: Dr Sarah Kuehne, School of Dentistry
Secondary supervisor: Dr Freya Harrison (Warwick) and Dr Erin Connelly (Warwick)
Project title: Natural products to promote a healthy oral microbiome
Dental plaque is the name given to the biofilm that develops on oral surfaces, especially tooth surfaces. It consists of a complex community of microorganisms, predominantly bacteria, embedded in a matrix of polymers of microbial and host origin. Dental plaque is present throughout life, and for the great majority of the time exists in a benign relationship with the host. However, it is also the aetiological agent of the two most common diseases affecting humans in the developed world – dental caries (tooth decay) and periodontal (gum) disease. In the case of gum disease, excessive plaque accumulation at the tooth/gum interface leads to inflammation known as gingivitis, which can progress to more serious periodontitis, and ultimately can lead to tooth loss. Gum health can be maintained by diligent, regular oral hygiene (usually including brushing with toothpaste and interdental cleaning such as flossing etc.) by reducing the burden of the dental plaque biofilm. However, many consumers fail to consistently undertake this hygiene regime, and thus oral care products such as toothpaste and mouthwashes are often supplemented with antimicrobials such as metal ions, surfactants or agents such as Triclosan, chlorhexidine or cetylpyridinium chloride. These approaches have been shown to be safe and effective in reducing rates of gingivitis in clinical trials and are used around the world in oral care products. However, consumers are increasingly looking for more naturally-derived products in order to manage their general and oral health needs. In parallel, the trend towards more nuanced messaging such as “working with your body” rather than more unsubtle approaches “kills 99.9% of germs” has also grown apace. However, there is a shortage of natural products which are both well understood and proven to be efficacious with respect to oral healthcare.
The overall objective of this project is therefore to identify and investigate the opportunities that natural products might have to deliver a range of benefits to help consumers manage their daily plaque control needs. A good source of candidate natural products for this application can be found in the plants and other natural substances used in traditional and historical medicine.
Medieval manuscripts contain numerous remedies for mouthwashes used to manage various aspects of oral health including ulcers, halitosis, inflammation and sores. Medieval infection remedies use ingredients known to possess some effects on bacterial growth, viability and signalling. Further, these recipes prescribe complex preparations of multiple ingredients, with contingencies of treatments for the same symptoms, which is consistent with extensive medical knowledge gained from a tradition of observation and experimentation. Our preliminary data demonstrate the great potential to derive molecules with potential for managing the biodiversity and community function of the oral microbiome from natural products found within the multi-component remedies of historical sources [see References below].
This PhD project will work within an interdisciplinary framework using skills from textual and data analysis (dry component) in combination with laboratory application and commercial industry to produce a pool of candidate natural products from these remedies which could modulate the oral microbiome to promote health, and could be developed into consumer products in the future.
The objectives are:
- To develop a list of oral health relevant natural ingredients, this would include cross-referencing natural products from the manuscript sources with a list of desirable qualities based on industry need and restrictions, and suggest good ones for lab exploration
- To evaluate how these affect structure and function of a simple model oral microbiome (Streptococci, Fusobacteria, Prevotella spp., Porphyromonas spp.). e.g. assess effects on species diversity, pathogen invasion, cell-cell signalling and metabolic outputs (e.g. volatile sulphur compounds that contribute to bad breath).
- To develop an understanding of additive, synergistic and antagonistic relationships when combining natural ingredients and with common excipients used in oral care products (e.g. antiseptics like chlorhexidine, flavour compounds).
- Carr VR, Witherden EA, Lee S, Shoaie S, Mullany P, Proctor GB, Gomez-Cabrero D, Moyes DL. Abundance and diversity of resistomes differ between healthy human oral cavities and gut. Nat Commun. 2020 Feb 4;11(1):693. doi: 10.1038/s41467-020-14422-w. PMID: 32019923; PMCID: PMC7000725.
- Connelly E, del Genio CI, Harrison F. Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents. Mbio 11, e03136-19 (2020)
- Connelly E. A Case Study of Plantago in the Treatment of Infected Wounds in the Middle English Translation of Bernard of Gordon’s Lilium medicinae. In: New Approaches to Disease, Disability, and Medicine in Medieval Europe, Studies in Early Medicine series, eds, Connelly E, Künzel S. (Oxford: Archaeopress, 2018).
- Harrison F, Roberts AE, Gabrilska R, Rumbaugh KP, Lee C, Diggle SP. A 1,000-Year-Old antimicrobial remedy with antistaphylococcal activity. MBio 6, e01129 (2015).
- Harrison, Freya and Connelly, Erin, ‘Could Medieval Medicine Help the Fight Against Antimicrobial Resistance?’ in Chris Jones; Conor Kostick; and Klaus Oschema (eds), Making the Medieval Relevant (Berlin: De Gruyter, 2019)
- Watkins F, Pendry B, Sanchez-Medina A, Corcoran O. Antimicrobial assays of three native British plants used in Anglo-Saxon medicine for wound healing formulations in 10th century England. J Ethnopharmacol 144, 408-415 (2012).
BBSRC priority area: Understanding the Rules of Life: Microbiology & Integrated Understanding of Health: Diet and Health
Techniques used in this project:
Techniques you will use include general microbiology culture experiments (planktonic culture, biofilm models and 3D cell culture community models); metabolomics using NMR or GC-MS; qPCR and other quantitative methods to measure gene expression and production of bacterial exoproducts known to promote or reduce health; and microscopy.
Contact: Dr Sarah Kuehne, University of Birmingham