In Europe, more than 6% of children and more than 3% of adults are affected by food allergies. Research in this field is going well and the intestinal microbiota quickly appeared as an interesting lead. Some of these bacteria produce a compound, called butyrate, which shows great promise for treating food allergies. Unfortunately, it is very unpleasant to take orally. Researchers at the University of Chicago have found another way to deliver this compound to allergy patients.
The prevalence of food allergies has increased dramatically over the past 20 years, especially in developed countries. Eggs, peanuts, cow’s milk, shellfish, or even nuts are among the most common allergens. Although unpleasant, the symptoms are relatively mild and easy to relieve in most cases (itching in the palate or throat, hives, allergic rhinitis, abdominal pain, etc.). In some cases, however, they require emergency intervention (pharyngeal edema preventing breathing or anaphylactic shock).
Some of the bacteria in the intestinal microbiota, the Clostridia, produce butyrate, a short-chain fatty acid that promotes the growth of “good” bacteria and thus preserves the intestinal mucosa. If an individual’s microbiota is out of balance (known as gut dysbiosis) and lacks these butyrate-producing bacteria, fragments of partially digested food can leak out of the gut and produce an immune reaction that results in allergic response. One avenue of treatment was to administer the missing bacteria orally or by fecal transplant, but clinical trials proved inconclusive.
Polymer micelles to encapsulate the metabolite
The researchers then thought of administering directly to patients suffering from food allergies the metabolite produced by these bacteria, namely butyrate. ” But butyrate has a very bad smell, similar to dog feces and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it. », explique le Dr Shijie Cao in a press release from theAmerican Chemical Society. But that’s not the only problem: if someone managed to swallow it, the compound would be digested before it even reached its target (the lower part of the intestine).
To circumvent these obstacles, Cao and his collaborators have developed a new mode of administration of this metabolite. They polymerized butanoyloxyethyl methacrylamide — a molecule whose side chain has a butyrate group — with methacrylic acid or hydroxypropyl methacrylamide. The polymers thus obtained are assembled into aggregates, or “polymeric micelles”: these micelles, regarding 30 nanometers wide, adopt a conformation such that the butyrate is trapped in their heart – which masks the unpleasant odor and taste of the compound.
Chemical composition and structural characterization of polymeric micelles containing butyrate. © R. Wang et al.
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Chemical composition and structural characterization of polymeric micelles containing butyrate. © R. Wang et al.
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Chemical composition and structural characterization of polymeric micelles containing butyrate. © R. Wang et al.
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Chemical composition and structural characterization of polymeric micelles containing butyrate. © R. Wang et al.
” data-medium-file=”https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite-300×185.jpg” data-large-file=”https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite.jpg” src=”https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite.jpg” alt=”micelles polymères métabolite” width=”725″ height=”446″ srcset=”https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite.jpg 725w, https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite-300×185.jpg 300w, https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite-500×308.jpg 500w, https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite-374×230.jpg 374w, https://trustmyscience.com/wp-content/uploads/2022/08/micelles-polymeres-metabolite-390×240.jpg 390w” sizes=”(max-width: 725px) 100vw, 725px”/>
The micelles also help protect the butyrate from gastric juices long enough for it to reach its destination. More specifically, the researchers created two types of micelles: one (denoted NtL-ButM), has a neutral electrical charge, and the other (Neg-ButM) bears a negative charge. This difference in charge results in the release of butyrate in different regions of the gastrointestinal tract.
The team tested this method of administration on 80 mice whose digestive system had previously been deprived of butyrate-producing bacteria (via antibiotic treatment). These mice were then made allergic to peanuts. Half of them were treated with the butyrate micelles, twice a day for two weeks; the other half, used as a control group, received a saline solution. At the end of the treatment, all the mice were fed with 1 mg of peanut protein.
An approach applicable to other inflammatory diseases
The protective effect once morest allergies was confirmed: thus exposed to peanuts, the mice treated with the micelles did not show an anaphylactic reaction, unlike the control group. A particularly encouraging result for Dr. Cao: “ This type of therapy is not antigen specific. In theory, it can therefore be applied to all food allergies by modulating gut health. “, he underlines.
As expected, butyrate was indeed released in the lower intestine; the remaining polymers were eliminated normally in the faeces of the rodents. Researchers observed that the treatment restored the gut’s protective barrier and rebalanced the microbiome by increasing the production of harmful bacteria-killing peptides, thereby promoting the proliferation of butyrate-producing bacteria. They noted that administering both types of micelles together produced the best results.
This treatment might therefore one day counter many types of food allergies, and even other inflammatory diseases. Butyrate has also shown therapeutic potential in the prevention of certain digestive pathologies such as inflammatory bowel disease, diverticulitis or irritable bowel syndrome.
The team now plans to conduct other trials on larger mammals, with other antigens, and then on humans. If the effects of the polymeric micelles are verified and the treatment obtains a marketing authorization, it might be marketed in the form of small sachets of powder to be mixed with water. But the researchers are also studying another route of administration, by injection. This method would indeed allow micelles to accumulate in the lymph nodes — an approach that has been shown to be effective in treating peanut allergies in mice.
The administration of micelles by injection would also make it possible to act more locally once morest an allergic reaction – therefore to suppress immune activity in a more targeted manner. This method might be used in particular in transplant patients (to avoid rejection) or in patients suffering from a localized autoimmune and inflammatory disease, such as rheumatoid arthritis.
