Reports of research work funded by grants prior to 2015
Malaghan Institute of Medical Research
Nutritional Intervention Strategies for Allergic Skin Inflammation
LWJ van den Elsen
This project is devoted to identify the pathways involved in the prevention and/or suppression of symptoms by a synbiotic diet (containing pre- and probiotics) in a mouse model for atopic dermatitis (AD), induced by topical application of the vitamin D analogue MC903 on the ears. MC903 induces TSLP production from keratinocytes and triggers allergic skin inflammation similar to AD. The outline was based on preliminary results that had shown that the synbiotic diet is effective in the suppression of allergic skin inflammation. The diet caused a reduction in the allergic skin response as well as TSLP and IL-33 production (serum and ear homogenates). Hence, this diet seemed a potential therapeutic approach to prevent or treat AD and the subsequent atopic march. Both have an enormous impact on the quality of life of patients and are a great financial burden for the New Zealand society.
To unravel the signalling pathway involved in the suppression of AD symptoms we are planning to use NanoString technology to study gene expression in 561 genes simultaneously in ear tissue. This can help to identify a new biomarker for AD. Furthermore, our goal is to study the connection between the gut microbiota and the immune system. We want to examine whether dietary intervention can improve allergy predisposing gut microbiota using 16S rRNA sequencing.
Unfortunately the results obtained with the synbiotic diet have been inconsistent. We hypothesise that the different manufacturing process used for the second batch of animal chow may have caused this. In the process of pressing the pellets, a part of the bacteria does not survive. Unfortunately we do not know how many live bacteria the end product of the new manufacturing technique contains and how this relates to the first batch of diet. Furthermore, the quality of the diet and amount of live bacteria present might decrease over time with storage of the product. This might be represented in the inconsistent results found for our experiments.
As we think the problem is in the administration of the probiotic bacteria, we would like to try a different way of delivering probiotics. We propose daily preparation of a porridge (based on methylcellulose and sucrose) in which we mix the probiotic bacteria. This will ensure the administration of live bacteria. The other advantage of this strategy is that the mice will get trained to eat the porridge as a bolus administration in less than 30 minutes, rather than spread out over the consumption of all chow. This is more similar to the human situation. Control mice will get to eat porridge without probiotics. This method has been proven to be cheap and effective by collaborators.
We would like to try the administration of probiotics in porridge (5 days/week) in the topical MC903 model for atopic dermatitis. If we can obtain a robust beneficial response using this approach we will use ear samples to investigate gene expression with NanoString technology, and caecal content for 16S rRNA sequencing to identify the mechanisms involved.
Despite the unforeseen results we hope to get a positive outcome with the different administration of probiotics. Even with these unexpected delays the completion of this project is still achievable within the 18-month time frame suggested.