Probiotics or Antibiotics to Cure Allergy

FUNDED: JANUARY 2018

FUNDED BY: The generosity of LJI Board Member Larry Spitcaufsky and Tiki Spitcaufsky

What was the goal of your SPARK project?

Over the last decades, the incidence of chronic immune disorders such as food allergies, eczema, asthma, type 1 diabetes, and multiple sclerosis has skyrocketed. Through association studies in humans and experimental animal models, we know that chronic inflammatory disorders are linked to the microbiome in humans and that changes in microbiota (dysbiosis) can cause disease in animal experimentation models. The SPARK project was designed to profile the microbiome in patients during the “atopic march”, a term referring to the typical progression of allergic diseases from skin (atopic dermatitis) to gut (food allergy) to lung (asthma) during early life. The overarching goal is to identify a “protective” versus “pathogenic” microbial signature that can be targeted in therapies to halt allergic diseases.

SPARK project results:

We sequenced stool samples of four atopic march patients matched with healthy controls and were able to see a striking 6.54-fold decrease in alpha diversity in the allergic patients as compared to healthy controls. This indicates a decrease in microbial diversity with predominant microbe species abundantly present in allergic stools compared to healthy ones. Regarding the skin, we observed a clear dysbiosis within the same atopic march individual (history of eczema, asthma) that had contact urticaria on the left arm but not on his right arm, which didn’t develop an allergic reaction. Interestingly, the same dysbiosis was amplified in eczematous skin with three predominant microbes abundantly homing the skin. These results are very encouraging, as it clearly indicates a direct relationship between dysbiosis and allergy, observed in localized contact urticaria and amplified in eczema.

What’s next for this project?

In addition to expanding our human studies, we will introduce pathogenic microbiomes into allergy-resistant rodents to study whether dysbiosis alone is sufficient to promote atopic diseases. Vice versa, we will treat allergy-sensitive strains with antibiotics that suppress the pathogenic microbiome, or promote beneficial dysbiosis by supplementing their diet with probiotics to test for disease reversal when a healthy microbiome is restored. Finally, we will use Multiple Reaction Monitoring mass spectrometry technology to profile the microbiome and immune responses at the protein level (complementing the genomic approach we will first adopt). The idea is to form a library of microbial metabolites that could potentially serve as drug targets in human therapies to halt allergic diseases, with little to no side effects considering their prokaryotic origin. If successful, the follow up study should confirm the hypothesis that microbial dysbiosis can exacerbate if not cause atopic diseases, and whether developing selective therapies to change the microbiome can benefit patients with allergies.

What’s next for Rana?

Next spring, I will start a position as Assistant Professor at the Cincinnati College of Medicine/Cincinnati Children’s Hospital Medical Center. The data I collected as part of my SPARK project allowed me to successfully compete for a Mucosal Immunology Study Team grant from the National Institutes of Health and will form the basis for a larger NIH grant, which I plan to submit as soon as I move to Cincinnati.