As many as one in ten people across the world have a food allergy of some kind, and life doesn’t get any easier once you develop one. You check the menu twice, you quiz the waiters, you scan the small print in the supermarket, and you look suspiciously at anyone offering you a biscuit. Every meal becomes a risk management assessment, with all the stress that comes with it. It’s not an ideal lifestyle, to say the least, which is why scientists are constantly trying to figure out new ways to tackle allergies and maybe even cure them.
In a new study, researchers describe a more palatable delivery method for “polymeric micelles”, which contain metabolites produced by beneficial gut bacteria. These compounds foster a healthy microbiome and repair the lining of the gut, proving effective at treating peanut allergies in mice.
A stinky cure
An allergy is an exaggerated response of the body’s immune system to normally harmless substances, such as pollen, foods, or house dust mite. This hypersensitivity causes the body to overreact by producing a disproportionate immune response when contacting an allergen. When the body has an allergic reaction to certain foodstuff, the immune system produces immunoglobulin E (IgE) antibodies, which are what cause allergic symptoms, including shortness of breath and wheezing, as well as potentially fatal anaphylaxis.
It’s not clear what causes allergies or why some people are more predisposed than others. Studies so far have linked both genetic and environmental factors to allergies, and as many as 45 percent of adults develop an intolerance to a foodstuff during their lifetimes. Allergies are, in fact, on the rise regardless of gender or ethnic background. According to the findings of a 2017 study, the incidence of shellfish allergies in the U.S. has increased by 7 percent, tree nuts by 18 percent, and peanuts by 21 percent. Shellfish and peanuts are also among the most common food allergies overall.
One of the ways people can get allergies is because of a poor gut microbiome — a bustling community of trillions of bacteria, archaea, fungi, and viruses, containing at least 150 times more genes than the human genome.
“Lots of things that people don’t think about, like depression or anxiety, are very clearly modified by your gut microbes. Appetite and the ability to digest food are modified by gut microbes. The key finding recently is the link with the immune system. Basically, the gut microbiome is controlling it, sending signals, because most of your immune system is in your gut, helping you fight infections, such as Covid and early cancers, that the immune system is picking off,” Professor Tim Spector, an epidemiologist at King’s College London and author of two books on dietary and gut health, told The Guardian in an interview.
When the microbiome is unhealthy, previous research has shown that it often lacks butyrate, a common metabolite produced by gut bacteria. In people whose guts lack this compound, there’s a significant risk that fragments of partially digested food can leak out of the gut and produce an immune reaction, thereby triggering an allergy.
In such situations, the treatment is to provide the missing bacteria that produce butyrate, most commonly orally. There’s just one problem with this idea: people just can’t stand butyrate.
“Butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” says Shijie Cao from the University of Surrey in the UK. “And even if people could choke it down, butyrate would be digested before reaching its destination in the lower gut.”
Given butyrate’s foul reputation, Cao and colleagues sought to make the compound more tolerable. They mixed butyrate-containing polymers together, which self-assembled into aggregates known as polymeric micelles. These aggregates have tucked-in butyrate chains in their core, cloaking the repugnant smell and taste.
During an experiment with mice lacking either healthy gut bacteria or a properly functioning gut lining, the polymeric micelle treatment was found to have restored the gut’s protective barrier and microbiome. Scientists think this is due to the increased production of peptides that neutralize harmful bacteria, thus making more room for butyrate-producing bacteria.
Most importantly, the butyrate-based treatment prevented anaphylactic response in allergic mice exposed to peanuts. But the procedure can likely work for any kind of allergy because the therapy is not antigen-specific.
Next, the researchers hope to conduct clinical trials if the U.S. Food and Drug Administration gives the green light to go ahead with an oral treatment. The plan is to pack the micelles in powder form inside a container. Consumers would simply tear open a package and stir the contents inside a glass of water or juice. They are also working on an injectable version that could suppress immune activation locally, which could prove useful for patients undergoing an organ transplant.
The findings were presented at the fall meeting of the American Chemical Society (ACS) held this week at the University of Chicago.
