Jeanelle Boyer, PhD and an FPIES Research Update

Have you ever looked back upon your life and been in awe as to how everything seems to have worked out for some higher purpose? I am still amazed at how many of my life choices were, unknowingly, preparing me to be the mom of an FPIES baby.  A PhD in nutrition, years teaching microbiology, a perfectly timed conference on the human microbiome, and a faculty position in Health Science at Keene State College were all invaluable as I struggled to find ways to help my little girl.  But, my daughter truly has been my greatest teacher.  She has brought me so much joy and has led me on the most amazing journey into health, wellness and all things microbiome.

Just over three years ago, my healthy, happy baby was born by emergency c-section.  She slept wonderfully, was breastfeeding like a champ and had that super soft, pink baby skin.  Unfortunately, all of this changed suddenly after a round of antibiotics for an ear infection at 6 weeks old.  All of a sudden, mild “spitting up” turned into severe GERD, she squirmed and wiggled all night unable to sleep, and she developed eczema on her entire body.  And the diapers….I will just say that they were not pretty!  It took a while, but we soon realized that she was allergic to everything that I was eating.  After months on severe elimination diets, we eventually switched to a hypoallergenic formula, and I finally had my happy baby back!  Normal diapers, soft clear skin, and comfortable sleep all night long!  Eventually, Ella was diagnosed with FPIES and we have been slowly trialing foods for the past three years.  It took her awhile to tolerate anything, but overtime she has gained foods and is now happily eating about 30+ foods. 

 I was exposed to antibiotics during pregnancy and during childbirth, and Ella was exposed as an infant.  Although not all FPIES parents have a similar story, I was amazed at just how many other parents did relate stories of antibiotic usage and concerns about “gut health”.  From all of my knowledge about the critical role that the microbiome plays in health, I couldn’t help but wonder if the microbiome was playing a role in her FPIES.  Luckily, I was in a position to actually test this hypothesis as part of my scholarship at Keene State.  Thanks to funding from the FPIES Foundation, Keene State College, NH-INBRE, and Ubiome and a wonderful collaboration with Dr. Yuan at Masss General, I have been able to design two studies that explore the connection between the gut microbiome and FPIES.

We have billions of bacteria living all over us with an especially high concentration of bacteria in our gut.  Recently evidence has been accumulating rapidly suggesting that these little microbes play a huge role in health and wellness.  Scientists all over the world are exploring the connection between the gut microbiome and allergy, autoimmune disease, GI disease, cardiovascular disease, and even neurological disease.  It is truly amazing!  Unfortunately, we have been living in a society that is pretty hard on our microbiome.  Changes in diet, an increase in antibiotic usage, less time spent in nature, and the abundance of antimicrobial compounds in the environment, have all led to decreasing diversity in the gut microbiome.  The full extent of this problem is still being studied, but many researchers believe that this is causing an increase in inflammatory and allergic disease around the world. 

So, where are we now? With the help of two wonderful Keene State students, I have collected survey data and microbiome data from a group of infants with FPIES and group of infants that do not have any allergy.  We are in the process of analyzing the microbiome data, but are already seeing some interesting trends in the survey data.  For example, antibiotics usage was higher in FPIES infants compared to allergy-free infants, and interestingly, maternal antibiotic usage during pregnancy was also higher in the FPIES infants when compared to the allergy free babies.  

As we continue to analyze data from the first study, we have also launched a second study that looks at older children with FPIES.  FPIES families often hear that many kids outgrow FPIES around age three.  That is the case for many, but not all.  Previous research has shown that the infant microbiome tends to become more “adult-like” around the age of three.  I wondered if this shift in microbiome, might explain why some kids outgrow FPIES.  However, if some kids had a severe dysbiosis or some kind of opportunistic pathogen in the gut, perhaps they would not outgrow FPIES as easily.  To test this hypothesis, we have just launched a study to compare the gut microbiome (both bacterial and fungal) of children aged 3-9 with FPIES to kids who have outgrown FPIES.  To complete the study we will also be comparing both groups to allergy free children.  We are in the process of recruiting participants now, and are very excited to see the results of both studies!

As is the case with a lot research projects, we could not do this work without your help!  I am incredibly grateful for all of the support that I have received from the participants in both studies…but we still need more participants for the FPIES children study.  If you are interested in helping out with this research, see below for some ideas.

HOW THE COMMUNITY CAN HELP:

1. Participate in the project- if you have a child between aged 3-9 years old that has been antibiotic free for the past month and either 1) has FPIES 2) has outgrown FPIES or 3) is allergy free, then you could potentially join the study!  Participation involves taking one or two stool samples from toilet paper using a provided kit and completing an online survey.

2. Spread the word- share with friends and family who may want to participate or share FPIES awareness.  Again, we need both FPIES and allergy free kids, so share with everyone!

Many thanks and best wishes to you all! I am confident that together we will figure out this crazy disease!

Please contact Maddy Carroll at madalyn.carroll@ksc.keene.edu. Or, you can also contact Jeanelle with questions at jboyer@keene.edu

This post was written and submitted by Dr. Jeanelle Boyer, who is currently researching the microbiome in the gut of infants affected by FPIES at Keene State College. To learn more about Dr. Boyer's background and her previous research work, please watch her webinar from FPIES Global Day 2016.

More Insights from the Global Patient Registry

More Insights from the Global Patient Registry

by Hilary Lagerwey 

Last year we shared some statistics gleaned from the data provided by FPIES families across the globe. The Global Patient Registry  is a platform to collect information such as medical history, family history, and specific symptoms. The purpose behind this data repository is to both help families glean some insights into this rare disease and also give researchers some direction so that the whole FPIES community can learn more. The information you all have already provided is invaluable and we are always looking for more people to take the surveys.

In our last report we examined what FPIES looks like so this year we decided to focus on medical and family history. Although no one knows exactly what causes FPIES, data such as this can possibly help further our collective understanding.

As you look through this data for yourself, it is important to note that these are informational survey’s and not collected in the same ways as other types of research such as a scientific study. The data comes from volunteer respondents and all of the information is patient/caregiver reported. Some families might be more likely than others to participate in the survey, and while this means the numbers here may skew towards the more severe and more protracted cases, we feel it is still important to give a voice to this group of FPIES patients. The more data we have the more we can learn and share with researchers. In sharing this information and analysis, our intent is not to present these statistics as conclusions, but as starting points for a discussion amongst the community. This article is just the beginning of these conversations!

When looking at statistics like this for a certain sub-population, in this case FPIES patients, it is most useful if you have a number to compare that to in the general population. For some of these numbers we do have a reasonable idea of how FPIES patients compare to the general population, and for some of these numbers we know less.

Again, keeping in mind that these are survey responses and not a specific scientific study, this information does not support the idea that birth circumstances (C-section births or prematurity) play a strong role in the development of FPIES. The percentages of C-section births and premature births are slightly lower for the FPIES population than the general U.S. population. (Note that this isn’t an examination of whether those numbers are statistically significantly lower, but they certainly aren’t dramatically higher.)

Looking at first degree relatives of FPIES patients (parents and siblings) can help get an idea of whether FPIES tends to cluster in families. Unfortunately at this time the prevalence of FPIES in the general population is not known so we have nothing to directly compare these numbers to, but as awareness spreads and research continues, perhaps we will soon know more about the overall prevalence. If we assume the population prevalence is less than 1 in 10 then this data might suggest a tendency for FPIES to cluster in families. The next question to ask would be does that clustering indicate a genetic component, or some sort of shared environmental factor such as the microbiome, or a combination of those factors?

These statistics that shows a seemingly high prevalence of GI disorders, metabolic disorders, and autoimmune disorders in the family history of FPIES patients, and especially the mothers, are perhaps the most interesting but also the least straightforward of this list. At first glance, this makes one question if there is some sort of genetic link here between GI disorders, metabolic disorders, and autoimmune disorders and FPIES. But we must also keep in mind that this is a pretty broad category of diseases so the number of cases you would expect in the general population is probably fairly high and also tricky to estimate for a number of reasons. 

It is also interesting that in our sample GI disorders, metabolic disorders, and autoimmune disorders seemed to disproportionately affect the mother. Does this suggest some sort of environmental factor in utero that contributes to FPIES? Or is this simply reflecting the fact that autoimmune diseases disproportionately affect women and the fact that women are more likely to go to the doctor and therefore more likely to be diagnosed with any condition? Or some combination of all of these things?

As you can see this data can be very useful and we as a community can help encourage more research so that we can all learn more. This data is very preliminary and these discussions are just the beginning. Please take the survey if you have not already so we can all continue to learn more!

This post is written by FPIES Mom and FPIES Foundation volunteer, Hilary Lagerwey.  Graphic created by FPIES Mom and FPIES Foundation volunteer, Melissa Rice.

A conversation with Prof. Stefano Miceli Sopo on the importance of a Global FPIES Patient Registry

Prof. Stefano Miceli Sopo works out of the Department of Pediatrics at Catholic University of the Sacred Heart in Rome, Italy. He has co-authored several studies on Food Protein Induced Enterocolitis Syndrome including:

• “Clinical management of food protein-induced enterocolitis syndrome”
•  "FPIES, From Practice to Theory"
• “Food protein-induced enterocolitis syndrome (FPIES) and well cooked foods: A working hypothesis” 
• “Ondansetron for Food Protein-Induced Enterocolitis Syndrome”
• “Chronic Food Protein-Induced Enterocolitis Syndrome Caused by Cow's Milk Proteins Passed through Breast Milk”

Prof. Stefano Miceli Sopo and his colleagues are passionate about FPIES research and the need for a Global FPIES Patient Registry. We recently had the opportunity to speak with Prof. Miceli Sopo who works with a center in Rome that follows and studies FPIES children.

Prof. Miceli Sopo says the most surprising thing for him is that there is still very little research being done on FPIES.  He says even most of the studies that are being done seem to offer only descriptions of case studies and maybe some guidelines.  He says, "We read little about the search for new treatments, to better understand its pathogenesis."  

Prof. Miceli Sopo says one of the most interesting recent aspects of FPIES research has to do with the promising effects of Ondansetron, during the acute phase of FPIES.  Ondansetron is an anti-vomiting medication, typically used to help chemotherapy patients.  He says in twenty of his case studies Ondansetron was administered and seemed to work well.

Prof. Miceli Sopo has made it a goal to create an FPIES registry in Italy and says there is a great need for a Global Registry, like the FPIES Foundation Global Registry.  He says, "It would be a really good thing" to have a central platform that was functional and affordable to provide information to pediatric allergy centers around the world.  He says a global registry would help doctors get on the same page when it comes to diagnosing FPIES.  Prof. Miceli Sopo says, "I believe there may be some differences.  We believe that we need a greater unanimity of behaviors.  The registry will serve to highlight the differences; we will try to eliminate them."

Prof. Miceli Sopo says hopefully a registry can also shed some light of what appears to be a spectrum of FPIES patients who suffer from varying degrees of the condition.  He says, "Just through the registry maybe we can see if there is a phenotype that tolerates small amounts of food, maybe processed in some way, and those who vomit after eating only a few milligrams of the food culprit."

Research of course takes time so Prof. Miceli Sopo says until we have more answers patients should keep an open dialogue with their doctors.  He says if there is any suspicion of FPIES he suggests eliminating the food, even if the suspicion is weak, and to carry out an Oral Food Challenge soon as possible.  Prof. Miceli Sopo says, "We have heard stories of children, who had 6-8 acute episodes before arriving at the diagnosis, it does not seem right."

If you interested in learning more about the Italian FPIES registry write to stefano.micelisopo@gmail.com

To join the FPIES Foundation Global Patient Registry follow this link.  If you've already joined you can instantly see survey and data results by clicking “View Data” here. 

This interview conducted and article written by Victoria Warren.  Victoria is a television news reporter for the NBC affiliate in Boston, WHDH-TV.  Victoria is a parent volunteer with The FPIES Foundation Volunteer Advisory Board.  Follow Victoria on twitter @VWarrenon7.