Investigations into potential dietary interventions in atopic dermatitis
Dairy Goat Co-operative （NZ） LtdMalaghan Institute of Medical ResearchAgResearch Ltd
摘要：Objective Children with Atopic Dermatitis（AD） have a higher risk of developing food allergies（’allergic march’） . Trials in infants have found reduced eczema with formula supplemented with specific prebiotics or probiotics . However, the mechanism of this dietary intervention has not been defined. Topical application of MC903, a Vitamin D3 analogue, in a mouse model induces changes in skin morphology and inflammation resembling AD . Using this model, we show that mice lacking functional mucosal-associated invariant T（MAIT） cells（MR1 knockout） have reduced inflammation and less pathology following MC903 application. The innate-like MAIT cells are abundant in mucosal tissues, recognise vitamin B-derived compounds produced by bacteria and yeasts and do not develop in the absence of microbial colonization（i.e. microbiome）. Microorganismderived vitamin B2 metabolites are stimulatory for MAIT cells, while folic-acid metabolites block MAIT cell activation. This suggests it may be possible to modulate MAIT cell activity by influencing the microbiota generating these metabolites. Methods As a proof-of-concept, we used a cross-sectional study to determine the phenotype of circulating MAIT cells in 120 healthy volunteers. Results We established potential associations with the gut microbial composition of each individual. Conclusions Our studies suggest MAIT cell activity, which can be influenced by the diet-microbiome axis, may be critical to diet-induced changes to health and disease both in the skin and the gut, and may be mechanistically involved in the ’allergic march’.