Allergy: A newborn's microbiota prevents hyper IgE antibody response to certain food antigens

Prevalence of allergy to food antigens is increasing in the world (alongside autoimmune diseases). Many believe it has to do with changes in microbiota composition due to environmental and processed food effects. But we still don't know how exactly microbiota prevents immune dysregulation characteristic of allergy or autoimmunity.     

For the past couple of years the team from South Korea has published several important papers addressing the role of microbiota and food antigens in modifying the gut immune system. This week they published yet another relevant paper in Science Advance. Below I present the highlights of the study.   

For this study the authors compared the level of IgE in sera from conventional mice fed regular diet, germ-free mice also fed regular sterile diet and germ-free mice fed with sterile antigen-free diet. As seen in the figure below GF mice develop, over time, hyper IgE condition. However, this effect was abolished in GF mice fed antigen-free diet. It indicated that antigens found in food interact with the immune system differently in the absence of microbiota.        

This was confirmed in reciprocal experiments where GF mice were introduced to the antigen-free diet or when antigen-free diet fed GF mice were introduced to a regular diet. In both conditions, a regular diet that contains antigens enhanced IgE level in the absence of microbiota.

Interestingly, the authors found that only certain food antigens, such as wheat gluten, could initiate hyper IgE response in absence of microbiota. Of note, the wheat gluten was shown to be digestion resistant.  

Another noteworthy observation was related to the age at which point mice were introduced to food antigens. Only young, but not older antigen-free fed mice, showed hyper IgE response when introduced to food antigens in the absence of microbiota. It indicated that there were some differences between young and older mice that made older mice resistant to hyper IgE production when responding to food antigens. 

So far we discussed how antigen-free fed mice respond to food antigens in the absence of microbiota. As expected, the introduction of microbiota to GF mice blocked hyper IgE response to food antigens.   

In summary, this study showed that in the absence of normal microbiota mice fed a regular diet that contains antigens will show hyper IgE response to certain food antigens. This response is abolished in GF mice fed antigen-free diet. The main question of how microbiota prevents IgE response or why certain food antigens are more immunogenic has not been addressed here. Also, the authors did not discuss it but it is important to mention here that hyper IgE response by itself does not mean pathological allergic response. The authors did not say that antigen-free mice fed regular diet became allergic to it (or to wheat gluten). It means that allergic sensitization requires additional mechanisms beyond hyper IgE response.

posted by David Usharauli