Select microbiota species provides protection against food allergy via RORγt+ Tregs

The body’s microbiota now unquestionably plays a significant role in preventing allergies, including food allergies. However, it is less clear exactly how the microbiota does it.

According to a recent study in mice that was published in Nature Medicine, the RORt + Tregs subset of the FOXP3 + gene family uses the adaptor MyD88 to protect against food allergies.

The majority of the experiments described here were carried out on genetically modified mice known as Il4ra^F709, which exhibit an allergy predisposition as a result of changes in IL-4 signaling. Here, germ-free Il4ra^F709 mice were colonized with a microbiota consortium that was enriched differently in infants who were not allergic or allergic. In Il4ra^F709 mice, a defined mixture of Clostridiales and Bacteriodales but not Proteobacteria was able to lessen allergic reaction. ( Note that you can expand the image by clicking on it to see it more clearly. )

The authors of a different set of experiments discovered that Il4ra^F709 mice, or mice that were specifically lacking in the RORt + Tregs subset, responded to allergic challenge by exhibiting similar phenotype. They believed there might be a link.

In fact, when colonized with a specific mixture of Clostridiales and Bacteriodales, Il4ra^F709 mice lacking the RORt + Tregs subset lost their ability to resist allergic reaction.

Last but not least, the authors attributed the loss of protection to the absence of MyD88 adaptor signaling in Tregs because Il4ra^F709 mice lacking this signal also displayed a lack of defense against allergic reaction when colonized with an established mixture of clostridiales and bacteria( Note, oral short chain fatty acid ( SCFA ) therapy failed to shield the mice from an allergic response.

Based on this and other studies, we could draw the conclusion that RORt + Tregs do play a significant role in preventing unwelcome inflammatory responses. However, the allergic sensitization protocol used in this study is not exactly” translational.”

The authors’ failure to investigate why Clostridiales and Bacteriodales but not Proteobacteria or other species could signal via MyD88 to provide protection against allergic response is one significant flaw in this study. In my opinion, what separates protective from non-protective microbiota species is not their innate signaling molecules, but rather their antigenic makeup, which gives RORt + Tregs epitopes to keep them active and in a good functioning state( MyD88 may be just what is required to maintain such antigen-specific Treggs active due to its role in metabolic pathways ).

written by David Usharauli