traitement allergie arachide microbiome souris

Peanut allergy successfully treated by modifying the gut microbiota in mice

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In Europe, food allergies affect more than 6% of children and more than 3% of adults. Research in this area is progressing well and the gut microbiota quickly emerged as an interesting lead. Some of these bacteria produce a compound called butyrate that shows promise for treating food allergies. Unfortunately, taking it orally is very uncomfortable. University of Chicago researchers have found another way to administer this compound to allergy sufferers.

The prevalence of food allergies has increased dramatically over the past 20 years, particularly in developed countries. Eggs, peanuts, cow’s milk, shellfish and nuts are among the most common allergens. Although uncomfortable, the symptoms are relatively mild and in most cases easily relieved (itching of the palate or throat, hives, allergic rhinitis, abdominal pain, etc.). However, in some cases they require emergency intervention (pharyngeal edema preventing breathing or anaphylactic shock).

Some bacteria in the gut microbiota, the clostridia, produce butyrate, a short-chain fatty acid that promotes the growth of “good” bacteria and thus protects the intestinal mucosa. When a person’s microbiota is out of balance (known as gut dysbiosis) and these butyrate-producing bacteria are absent, fragments of partially digested food can leak from the gut and trigger an immune response, resulting in an allergic reaction. One treatment option has been to give the missing bacteria orally or by stool transplant, but clinical trials have proved inconclusive.

Polymeric micelles to encapsulate the metabolite

The researchers then thought of directly administering the metabolite produced by these bacteria, namely butyrate, to patients with food allergies. ” But butyrate has a very bad odor, similar to dog poop and rancid butter, and it tastes bad too, making people unwilling to swallow it. ” says Dr. Shijie Cao in a statement by 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 destination (the lower part of the intestine).

To circumvent these obstacles, Cao and his collaborators developed a new way of administering this metabolite. They polymerized butanoyloxyethyl methacrylamide—a molecule whose side chain has a butyrate group—with methacrylic acid or hydroxypropyl methacrylamide. The resulting polymers are assembled into aggregates, or “polymeric micelles”: These micelles, about 30 nanometers wide, adopt a conformation such that the butyrate is trapped in their heart – masking the compound’s unpleasant odor and taste.

Chemical composition and structural characterization of polymeric micelles containing butyrate. © R. Wang et al.

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 (designated NtL-ButM) has a neutral electrical charge, and the other (Neg-ButM) carries a negative charge. This charge difference leads to the release of butyrate in different regions of the gastrointestinal tract.

The team tested this delivery method in 80 mice whose digestive systems had previously been stripped of butyrate-producing bacteria (by 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, which served as a control group, received saline. At the end of treatment, all mice were fed 1 mg peanut protein.

An approach that is applicable to other inflammatory diseases

The protective effect against allergies was confirmed: in contrast to the control group, the mice treated with the micelles did not show any anaphylactic reaction when exposed to peanuts. A particularly encouraging result for Dr. Cao: ” This type of therapy is not antigen specific. In theory, therefore, it can be applied to all food allergies by modulating intestinal health. ‘ he emphasizes.

As expected, butyrate was indeed released in the lower gut; the remaining polymers were normally excreted in the rodents’ faeces. The researchers observed that the treatment restored the gut’s protective barrier and rebalanced the microbiome by increasing the production of harmful bactericidal peptides, thereby encouraging the proliferation of butyrate-producing bacteria. They found that administering both types of micelles together gave the best results.

This treatment could therefore one day counteract many types of food allergies and even other inflammatory diseases. Butyrate has also shown therapeutic potential in preventing certain digestive diseases such as inflammatory bowel disease, diverticulitis or irritable bowel syndrome.

The team now plans to conduct further studies in larger mammals with other antigens, and then in humans. If the effects of the polymeric micelles are verified and the treatment receives marketing approval, it could 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, injection. This method would actually allow micelles to accumulate in the lymph nodes – an approach that has been shown to be effective in treating peanut allergy in mice.

The administration of micelles by injection would also make it possible to counteract an allergic reaction more locally – i.e. to suppress immune activity in a more targeted manner. This procedure could 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.

Source: bioRxiv


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