Going with the Gut: Understanding the Role of Our Internal Microbiology in Developing and Regulating Food Allergy

Gary B. Huffnagle, Ph.D., the Nina and Jerry D. Luptak Research Professor at the Mary H. Weiser Food Allergy Center, spent most of his career as an immunologist and microbiologist focused on asthma before switching to studying the microbiome and how allergic immune responses develop, specifically how bacteria and yeast in our bodies participate in making us healthy or making us sick. Here he answers six questions about his work.

Gary Huffnagle
Gary B. Huffnagle, Ph.D., is the Nina and Jerry D. Luptak Research Professor at the Mary H. Weiser Food Allergy Center.

How would you describe food allergy research?

Food allergy is very different than any other disease that we’ve seen. It has some shared features with a number of other diseases, but more importantly, it has its unique features. There is much about food allergies that researchers do not understand. What we definitely know is that the way the immune system regulates itself, the way it controls its reactivity or non-reactivity, is defective. Something has gone completely wrong.

There are a couple of points in an immune response where that could possibly happen and which have been the focus of our research. One step is that when you eat something, your immune system treats it like a harmful invader and reacts to it: a problem in “sensitization.”

Another step is when the immune system pathways that normally keep a response from getting too strong are missing or they are dysfunctional: a problem in immune response regulation.

What areas of food allergy are you currently investigating?

For the past 15 years, I have focused on not the microbes from outside the body, and whether they are going to cause infection, but rather the microbes that are inside the body, the microbiome, and what role they play in how our body normally functions. Those microbes include bacteria, yeast and parasites.

With food allergies, there’s data emerging that some of these bacteria and yeast play a role in whether we stop ignoring a food that we eat and now we react strongly to it. Some of these bacteria and yeast normally play a role in shutting down immune responses that are too strong or they prevent immune sensitization against our food.

We’ve been focusing more recently on the role of yeast because they are largely understudied, and also the idea that one of the places that we don’t think much about as a site where problems can start is actually the stomach, an organ where there’s a lot of interaction with the microbiome.

We have evidence that, like the gastrointestinal tract, the stomach can be a site where immune responses to food develop, which definitely changes the nature of how we look at the regulation of immune responses.

Yeast can easily tolerate the acids and low pH of the stomach, so they can live quite happily there. We all carry yeast in our bodies: Sometimes there are high levels and sometimes there are low levels. We are studying how these yeast levels affect immune responses to food.

Why are you passionate about this area of research?

Because it is unexplored and the need for knowledge is great. Food allergies are an unregulated immune response to a non-harmful stimulus: food.

Our research focuses on one aspect of how the immune system is regulated, which is by the indigenous microbes of the body.

If we can identify the various aspects of the internal microbiology that can be either turned up or turned down to help curb food allergies, then we can focus on manipulations that we already know will change the microbiology of our bodies: dietary changes, dietary supplements, antibiotics, probiotics, and fibers.

“My sense of urgency is that if this is where we are now, fast forward 10 years from now, if we don’t do anything, are we going to be a whole lot worse? What’s behind all of these changes?”

Gary B. Huffnagle, Ph.D.

Why is food allergy research important?

We just didn’t have anywhere near this level of food allergies when I was growing up. My sense of urgency is that if this is where we are now, fast forward 10 years from now, if we don’t do anything, are we going to be a whole lot worse? What’s behind all of these changes?

What hope does your research represent for families?

The key to translating this discovery into treatment is first understanding more about what
goes wrong when the microbiome changes or the stomach becomes leaky. Then, we can investigate how to correct adverse changes in the microbiome and/or improve insufficient barrier function of the stomach.

Our focus is exploratory science whose goal is to push back the boundaries and identify and understand biological processes that we have not previously considered. This will provide the entire food allergy research field with new targets for prevention and therapy.

What do you wish people understood about food allergy?

People need to be aware and compassionate. Personally speaking, I think sometimes the fact that we call it food “allergy” diminishes how bad the problem is.

People talk about having seasonal “allergies” or “allergies” to things like mold. They take an inhaler and stay away from certain things and they are fine.

In sharp contrast, with a severe food allergy, you taste something and within minutes, you can begin to develop anaphylaxis and become critically ill.

A common food can be a toxin, a poison to someone with a severe food allergy. The food allergy epidemic needs to be taken very seriously.