Microbiome and Food Allergies: Therapeutic Potential of Beneficial Bacteria Living within Us

By Stacey Sturner
Regional Director, Midwest of End Allergies Together (EAT)

In the medical world, microbiome is the new black. Search the science pages of the internet or follow any allergy-aligned Twitter account and it is guaranteed that another microbiome-focused news article or research study will pop up. This is for good reason since it is a fascinating and relatively uncharted territory for exploration. If the bacterium-seeking scientists are right, it could uncover the root of numerous health conditions and specifically lead the field toward safer, more effective food allergy treatments.

Officially coined in 2001, microbiome describes a community of approximately 100 trillion cells, called microbes, located throughout the human body with the largest microbial quantities residing in the gastrointestinal tract. Immunoglobulin E (IgE)-mediated food allergy, meanwhile, is a malady caused by a misfiring of the immune system. However, digestion and intestinal health are increasingly being recognized as critical pieces of the food allergy puzzle. The crux of this intersection seems to lie within gut microbiome and ongoing research of it has indeed been preliminarily revealing of an association with allergic disease pathogenesis.

Genome Meets Microbiome

Microbiome is like the human genome – we all have it. Whereas genome is the complete genetic information of an organism, microbiome is the genetic information of microscopic living organisms termed microbiota. It is even frequently billed as “our second genome.” The Human Genome Project (HGP), an international research effort to sequence and map genes of the human species that concluded in 2003, ultimately paved the way to the Human Microbiome Project (HMP). Established in 2008, HMP was a five-year feasibility study that aimed to identify and characterize the microorganisms found in connection with both healthy and diseased humans via metagenomics (broad genetic perspective on single microbial community) and whole genome sequencing (deep genetic perspective on certain aspects of given microbial community). This data continues to be applied in the analysis of microbiome’s role in human health and disease. To date, 1,300-plus reference strains have been isolated from the human body and appropriately sequenced to aid in medical research investigating the influence of certain bacterium on behavior, immunity, mood and weight.

The White House joined the action in May 2016 by announcing the National Microbiome Initiative (NMI) to continue studying beneficial bacteria. With $121 million in federal funds and $400 million in private dollars, NMI is an ambitious plan to better comprehend the microbes that live in and on humans, other animals, crops, soils, oceans, etc. Microbiome, after all, is equally about humans’ complex relationships with the environment.

Headquartered in Chicago, The Microbiome Center is one of the commitments resulting from NMI in partnership with The University of Chicago, the Marine Biological Laboratory and Argonne National Laboratory. According to Dr. Jack Gilbert, Faculty Director of The Microbiome Center who also serves as an originator and core group leader for NMI, “This will be the premier site in the U.S. to perform microbiome research and build solid translational initiatives at the forefront of microbial therapies. We have an extensive group of researchers interested in treating allergenic and other immune diseases in children and adults. These efforts are helping us to improve our outreach and coordinate larger, more diverse initiatives with the potential for bigger, and more immediate, impact.”

Hygiene Hypothesis Redefined

Microbiome is a key component of the prevailing hygiene hypothesis (HH), which asserts that lack of early childhood exposure to infections, microorganisms and parasites boosts vulnerability to allergic diseases. Why would this be? Ongoing research has shown that the exercise of diversified exposure helps work out immune systems to make them stronger (read: healthier). Like everything else allergy-related, the science behind this theory is significantly more complicated than the sum of its parts. Case in point, there has been a universal fixation and narrow focus on personal hygiene. Play in the dirt! Avoid hand sanitizer! This oversimplification of the HH does not do the theory justice. It is less about sanitation and more about the evolutionary, multi-generational depletion of environmental microbes.

“The hygiene hypothesis really has nothing to do with visible cleanliness,” explained Moises Velasquez-Manoff, internationally-renowned science writer and author of An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases. “One could think of it as the ‘sanitation hypothesis’ or the ‘microbial deprivation hypothesis’ or the ‘disappearing microbiota hypothesis’ – all of which have been proposed, and all of which I think are a little more precise than the HH.”

Dr. Martin J. Blaser agreed, “I call it the ‘disappearing microbiota hypothesis’ – not as simple to say as the HH, but I believe more accurate.” As Director of New York University’s Human Microbiome Program and Professor of Microbiology at New York University School of Medicine, Dr. Blaser literally wrote the book on this theory that is aptly titled, Missing Microbes: How the Overuse of Antibiotics is Fueling Our Modern Plagues.

Microbiome Modulating Pathways

So, this begs the question, where does bacterial-based research go from here to repair the massive microbial imbalance? The deeply intertwined problems progressed over the span of centuries; hopefully, the solutions will come to light at an accelerated pace. In fact, the news story du jour is about Cambridge, Massachusetts-based Vedanta Biosciences, a startup company converting bacterial strains into a new class of pharmaceutical drugs to fight infections and inflammation. These types of developments frequently make headlines of mainstream media because microbiome impacts a mass market and if harnessed correctly, it has the possibility to help everybody. Yes, everybody.

Fecal matter transplants (FMT), a procedure in which stool is collected from a tested donor and placed in a patient, are just the tip of the, err, iceberg. Confirmed to be effective for curing Clostridium difficile (C. diff), inflammation of the colon caused by bacteria, FMT are a promising treatment target for a myriad of other diseases involving intestinal dysbiosis. Food allergies fit into this scope of research, though still considered highly experimental.

The study of additional microbiome modulating therapeutics is extensively underway to determine their efficacy in preventing and treating atopic diseases, including food allergies. Probiotics, ingested live microbes that can alter intestinal microbial populations, may prove to be particularly valuable to children who have food allergies as published data illustrates that they have different intestinal microbiota than their non-allergic counterparts. For instance, novel forms of probiotics that go beyond yogurt-like Lactobacilli are currently being developed. The projected success of these therapies, worth noting, will depend on many variables, such as bacterium type, dosing regimen and delivery method.

Then, there is diet. “We have co-evolved with our intestinal bacteria for millennia. They eat what we eat. These commensal bacteria are required to break down insoluble dietary fibers that we cannot digest on our own. Specialized bacterial populations ferment these fibers to produce metabolites, called short chain fatty acids, which are essential for the health of the intestinal epithelial lining,” clarified Dr. Cathryn Nagler, Bunning Food Allergy Professor and Professor of Pathology at The University of Chicago. “Our 21st century diets are high in fat, sugar and processed foods and low in dietary fiber. Diet is one of the prime modern day demographic factors driving changes in the composition of our intestinal microbiota (dysbiosis) and depleting bacterial populations (and their products) which are important for our health.”

“We identified a particular population of mucosa associated bacteria (Clostridia) that protects against allergic sensitization to food by inducing a barrier protective response. These ‘peace-keeping’ bacteria are among the most potent fermenters in the gut and produce the short chain fatty acid butyrate from dietary fiber. The barrier protective response they induce reduces access of dietary allergens to the bloodstream (and the immune system) to promote tolerance to dietary antigens,” Dr. Nagler added.

Along these lines, Dr. Nagler and her team are presently working on two microbiome modulating approaches: 1) identification and characterization of dietary fibers that specifically expand butyrate producing Clostridia (for consumer-based use as a dietary supplement); and 2) creation of butyrate nanoformulations for development as a new drug-based therapy.

EAT Bites

In summary, microbiome research is the type of fashion that never goes out of style. Here are key takeaways:

A lot remains to be learned in this active and ever-expanding field of discovery with leading experts just beginning to scratch the surface.

• Increased financial support is urgently needed across various disciplines, especially food allergies, to continue moving the needle in a positive direction.
• This primer serves as a “living” document and, therefore, will be updated as new studies are published and progress is made.

Based in Fairfield, Connecticut, End Allergies Together (EAT) is a national non-profit organization dedicated to funding treatments and cures for food allergic disorders. Microbiome is one of several research focuses with 100% of every contribution going directly to the researchers in the trenches. For more information and/or to donate, please visit endallergiestogether.com.