Estudio

Do Sugars Have Any Role in Dermatology Today?

24/03/2020
Sugars, or carbohydrates, are the most abundant class of organic compounds found in living organisms. There are two major subfamilies; the simple sugars (monosaccharides) and the complex sugars (oligosaccharides composed of 2-10 monosaccharides and polysaccharides composed of more than 10 monosaccharides).

Previously sugars have mainly been known for their role in providing and storing energy, however, they have far more varied functions particularly with regards to the skin. They are widely involved in cell signalling associated with the modulation of inflammation and also play an important role in microbial adherence, colonisation and biofilm formation1. Glycotechnology encompasses the further exploration of these roles and how similar exogenous carbohydrates can be utilised in topical therapies to help control cutaneous infection and inflammation.

 

The Role of Sugars in Surface Microbe-Host Interactions

The skin is constantly exposed to potential pathogens but often these only pose a threat when the structure and/or function of the epidermal barrier is compromised. Skin infection results when microbes are able to adhere to host skin cells, proliferate and produce virulence factors. They achieve this using lectins; glycoprotein structures expressed on their cell wall or cell membrane pili which can recognise, and bind to, the skin sugars which are abundant on animal cell surfaces. Microbes themselves also harbour surface carbohydrates which promotes intracellular adhesion and therefore the formation of biofilms. Due to the importance of sugars in microbial adherence, a promising approach in dermatology is to use exogenous carbohydrates which mimic the naturally occurring ones. Instead of binding to the host cell, the microbial lectins recognise and bind to these exogenous carbohydrates instead, thus saturating binding sites and rendering them unable to adhere to host skin cells.  A number of in vitro studies have been published which demonstrate that specific saccharides can effectively inhibit and reduce microbial adhesion2,3.

The Role of Skin Sugars in Surface Immunity

Keratinocytes can become activated by exogenous factors, for example infections, irritants and allergens, and/or endogenous stimuli, such as cytokines released from the immune system. Once activated, these keratinocytes release a wide panel of cytokines such as interleukin-1 (IL1) and tumour necrosis factor alpha (TNFα), which in turn initiate the inflammatory cascade. Cytokines possess both a receptor binding domain (RBD) and a carbohydrate binding domain (CBD), the latter of which is a lectin and recognises specific sugars. This interaction is essential for the production of the immune signal, therefore blocking the CBD with exogenous sugars results in reduced pro-inflammatory cytokine stimulation. An in vitro study4 evaluating the modulation of canine keratinocyte activation demonstrated a greater inhibitory effect on the release of TNFα in the L-rhamnose solution (75% decrease) compared with a dexamethasone solution (56% decrease).  

In summary, the use of specific exogenous sugars can provide anti-adhesive and immunomodulatory benefits thus aiding in the management of cutaneous infection and inflammation. Utilising glycotechnology in topical formulations such as shampoos and ear cleaners, represents an innovative and useful addition to the armoury of dermatology therapies. 

1. Lloyd DH et al (2007) Role of sugars in surface microbe–host interactions and immune reaction modulation. ESVD and ACVD 18; 197–204
2. Bond R, Lloyd DH (1998). Studies on the role of carbohydrates in the adherence of Malassezia pachydermatis to canine corneocytes in vitro. Veterinary dermatology, 9, 105-109.
3. McEwan NA et al (2005). Sugar inhibition of adherence by Pseudomonas to canine corneocytes Veterinary Dermatology, 16, 204-205.
4. Ibisch C et al (2001). In vitro assays for keratinocyte activation: modulation by fucose, arabinose and rhamnose. In: Proceedings 18th ESVD-ECVD Congress, Copenhagen, Denmark, 155.