40% of Patients With Peanut Allergies Develop Tolerance in First Clinical Trial of Gut Microbiota Transplant

A clinical trial found that 6 of 15 patients with peanut allergies developed tolerance to peanut consumption after receiving a gut microbiota transplant. The case suggests the potential of treating food allergies with fecal microbiota transplantation (FMT) in the first clinical trial of the approach in humans.

The National Research Center for Biotechnology Policy reported the findings in a report published on the 8th, citing a paper published on the 5th of last month in the international journal Science Translational Medicine.

Food allergies affect up to 10.8% of U.S. adults. Standard treatment is limited to avoiding allergens and emergency measures such as epinephrine injections. Oral immunotherapy (OIT) also requires continued exposure to maintain its effects, which diminish when treatment is stopped.

The research team hypothesized that transplanting gut bacteria from healthy donors without allergies could ease hypersensitive immune responses. FMT is approved by the U.S. Food and Drug Administration (FDA) to treat recurrent Clostridioides difficile infection, but this was its first application to food allergies.

The 15 clinical trial participants took 36 odorless, tasteless capsules containing donor gut bacteria in a single dose. Before treatment, they experienced an immune response when they consumed more than 100 mg of peanut protein (less than half a peanut). Four months after treatment, one participant could consume 300 mg, and five could consume at least 600 mg (equivalent to about 2.5 peanuts).

The 9 participants who did not respond may have failed to establish the bacteria. Five of the 6 responders were men. The treatment was effective in 60% of participants who received antibiotics beforehand, compared with 30% of those who did not.

The research team transplanted participants’ fecal microbiota into germ-free mice and observed allergic responses to ovalbumin (OVA). Allergies were suppressed in mice that received microbiota from responders, but were induced in mice that received microbiota from nonresponders.

Bacteroides ovatus increased in responder mice, as did the primary bile acid cholate in their serum. Removing the bacterium’s bile salt hydrolase (BSH) eliminated the protective effect against allergies, confirming bile acid metabolism as a key pathway.

The research team considered the persistence of the effect for more than 4 months after a single dose a strength compared with existing treatments. The proof of concept linking human and mouse findings, along with the effect against egg antigens, suggests the approach could be extended to allergies beyond peanut.

However, this was an early-stage trial involving 15 people, with no placebo control group. A sex imbalance was also observed, but the researchers withheld conclusions because of the small sample. The team said a larger randomized, double-blind, placebo-controlled trial is needed and estimated that regulatory approval could take about 10 years. Registration for a second, larger clinical trial is nearing completion; the plan is to administer bacteria at about 12 times the dose, divided over 1 month.