Microbiome Analysis and Probiotics for the Prevention and Treatment of Food Allergy and Atopic Dermatitis

The prevalence of allergic diseases is increasing rapidly for reasons that remain unclear, but it is now evident that gut microbiota are involved in this phenomenon. Cecilia Berin, PhD, from the Mount Sinai School of Medicine, New York, discussed the ways in which the microbiome regulates food allergy and atopic dermatitis at the American Academy of Allergy, Asthma and Immunology’s 2015 annual conference in Houston, TX.

She began her talk by reviewing several pathways in the mucosal immune system that regulate tolerance and allergy to foods. Data obtained from studies that evaluated germ-free mice and recolonized germ-free mice confirmed that the gut microbiota has a major impact in these pathways and in the development of sensitization in the gut as well. What is less clear is how shifts in the number or constituents of the gut microbiota may influence the balance between food tolerance and allergy.

Berin then discussed two papers that provided direct evidence for dysbiosis, or microbial imbalance, in food allergies. In 2015, researches evaluated, in a birth cohort study, infants who were allergic to food. By 16s sequencing, they showed that the gut microbiome had lower microbial richness at three months of age. They also found changes in the microbiome’s makeup at three and twelve months of age. Surprisingly, no changes were observed in Clostridia. The other study, from 2014, did not find changes in the microbiome diversity of children with food allergy, but the fecal content had a different microbiota composition.

In addition, they observed a positive correlation between Clostridium and serum-specific IgE. She also mentioned that innumerous studies evaluated other atopic outcomes early in life, when sensitization to food happens. The common finding in these studies is that decreased microbial diversity early in life is a predisposing factor to the development of eczema and other atopic sensitization.

According to Berin, there are two possible scenarios, not mutually exclusive, for how the microbiome changes. The first hypothesis is that there are “good” and “bad” bacteria. The “bad” bacteria, like clostridium, promote the generation of regulatory T cells (Treg), which in turn suppress sensitization. The pro-allergenic “bad” bacteria produce immunoregulatory toxins that affect the gut barrier. The second hypothesis is that the microbiome diversity is the main protective factor. She speculated that increased antigenic stimulation, from diet or the microbiome, could increase the diversity of Treg in the gut and, consequently, the protective effect.

Lastly, she mentioned the mining of the human gut microbiota, a powerful approach to evaluate the role of the microbiome. In this technique, germ-free mice are reconstituted, or humanized, with extracts from human stools. The phenotypes of these animals are then analyzed. Recent data has shown that Treg induction in the colon is donor-specific.

At the end, Berin highlighted the following points: 1) there are differences in the gut and skin microbiota between those who do or do not develop food allergies; however, a deeper understanding is needed; 2) it is still not clear whether this is an issue of diversity versus “good/bad” bacteria; 3) a better understanding of the essential immunomodulatory effects of the bacteria is needed in order to know which pathways can be modulated by microbial therapy; 4) the protective features of bacteria are still not very clear.

Finally, she told the audience that it is not known yet if microbial therapy can be effective as treatment.