Progress on Treating Food Allergy: Manipulating the Bacterial Microbiome

As you all know, I am always on the look out for good news on the “what can we do about it now” front – or at least meaningful progress toward a solution.  I very much enjoyed an article yesterday in Scientific American on manipulating the bacterial microbiome to treat food allergy. It was a summary of some recent research and findings, but what I found almost most interesting, was the summary of some new companies and the products they are testing.[i]

The article starts by describing the research of Dr. Cathryn Nagler, at the University of Chicago, who is attempting to isolate the bacteria that can prevent allergic response. Last year, she demonstrated that giving fecal transplants of microbes from healthy, non-allergic human babies, can stop severe allergy in mice prone to such reactions.  Her “ah ha” moment came in 2000, when she read an article about how peanut-allergic mice had a genetic glitch which lead to damage to a receptor (TLR4) that appears on immune cells, and recognizes microbes.  The immune cells of these allergic mice then lacked the ability to “talk” to microbes in the gut.  Dr. Nagler realized then that those trillions of bacteria have the ability to suppress immune response by stimulating TLR4, and thus, alterations to the microbiome may lead to a lack of that communication…and allergy.  And of course, with our shifts in lifestyle (i.e.  the biome depletion paradigm, caused by our lack of exposure to our old friends in our industrialized, modern societies), these alterations are all too ubiquitous.

In 2004, Dr. Nagler showed that indeed, mice with defective TLR4 receptors went on to develop severe peanut allergy (anaphylaxis); those with normal receptors did not.  But when gut bacteria were wiped out with antibiotics, even the “normal” mice went on to develop the allergy.

In recent work, Dr. Nagler and her team have discovered that Clostridia prevent food allergy in germ-free mice, she believes by stimulating the production of regulatory T-cells (which modulate inflammation) and the production of IL-22, a molecule well-documented to protect the gut epithelial lining.  She theorizes that if protective bacteria are missing, the integrity of the gut barrier is compromised, which (by letting food particles into the blood stream), triggers allergic response.  It turns out that top food allergens (casein (dairy protein), eggs, peanuts, tree nuts, soy, wheat, fish and shellfish) have something in common:  they are resistant to digestion.  Says Dr. Nagler:  “’That seems to be what makes peanut the champion—its ability to resist degradation in the gut…’”

Other researchers have shown, by comparing babies with allergy to those without, consistent alterations in the gut bacteria in the former.  One study tracked 226 children with milk allergy from infancy until they were 8 years old.  The scientists found that certain bacteria, including Clostridia, were enriched in the stool of 3-6 month old babies who outgrew their allergy, as compared to those who did not outgrow it.  This difference though did not exist in older children.  The conclusion:  “…allergy-protective microbes may only act early in life.”

Back to the work of Dr. Nagler then:  her team has isolated the Clostridia species, Anaerostipes caccae.  Another team of scientists at Boston Children’s Hospital found that the species Subdoligranulum variabile and a set of Clostridia species prevented allergy.

So where is all this going, in terms of actual products that can help actual people?

1. There is a small clinical trial ongoing at the moment, using FMT to treat people with peanut allergy.
2. Another clinical trial is ongoing on those species identified by the Boston Children’s Hospital group, which may lead to a live microbial product to treat food allergies.
3. Vedanta Biosciences, in Massachusetts, is also developing a probiotic capsule with a mix of Clostridia strains selected for their ability to induce the production of regulatory T-cells.
4. An Australian Company, Prota Therapeutics, is creating a peanut allergy product, using peanut immunotherapy (tiny amounts of peanut protein) combined with a particular species of Lactobacillus.
5. Nagler herself has co-founded a startup company that is developing a combination pill of live probiotics combined with the short-chain fatty acid, butyrate, which is particularly good for gut barrier function, as my regular readers know. Their clinical trial is due to start next year.

So…perhaps help is on the way.  Considering that the prevalence of food allergy – which is already frighteningly common – is growing yearly, that is a really good thing.  I’ll watch for the results of these trials over the next year or two!

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[i] https://www.scientificamerican.com/article/gut-microbes-may-be-key-to-solving-food-allergies/