Nonallergen-specific Treatments for Food Allergy

Jay A. Lieberman, MD; Julie Wang, MD

Disclosures

Curr Opin Allergy Clin Immunol. 2012;12(3):293-301. 

In This Article

Probiotics and Prebiotics

Probiotics and prebiotics have been studied at length as a means of both prevention and treatment of atopic diseases. Most of the randomized, clinical trials using probiotics have examined their effects on atopic dermatitis;[32–38] however, there are a few studies that have examined their effect on food allergy. Here, we review only those clinical trials that report data on food allergy outcomes since the publication of the most recent review on the topic in this journal.[39] When interpreting these studies, it is important to note that the study population, microorganisms used, doses, and durations of therapy can vary greatly.

Murine Model

Schiavi et al.[40] examined a probiotic mixture of eight different bacterial strains (Lactobacillus acidophilus, Lactobacillus delbrueckii, Lactobacillus casei, Lactobacillus plantarum, Bifidobacterium longum. Bifidobacterium infantis, Bifidobacterium breve, and Streptococcus salivarius) in a shrimp tropomyosinsensitized mouse model. The authors found that treatment with the probiotic mixture after sensitization could decrease anaphylaxis scores upon antigen challenge, with a concomitant decrease in fecal histamine levels as compared with sham-treated controls. This effect was associated with a decrease in tissue levels of Th2 cytokines and an increase in the tissue levels of regulatory cytokines.

Human Studies

Human studies of probiotics for atopic diseases have not been very conclusive to date, and the most recent Cochrane review of probiotics for eczema concluded that there was evidence to suggest that probiotics were not effective in treating eczema.[41] As stated earlier, there are even fewer data on their use in food allergy. A recent randomized trial of Lactobacillus GG in an extensively hydrolyzed casein formula (EHCF) compared to EHCF alone demonstrated that infants on the supplemented formula developed tolerance to cow's milk at a faster rate.[42] In perhaps the best trial of probiotics in food allergy to date, Hol et al.[43] examined the use of probiotics (Lactobacillus casei and Bifidobacterium lactis, each at 107 colony-forming units/gram of formula) in children with diagnosed cow's milk allergy using a randomized, double-blind, placebo-controlled design. The authors showed that there was no difference in the development of tolerance to cow's milk after 6 or 12 months of treatment between the probiotic and placebo groups, based on double-blind, placebo-controlled oral food challenges. In addition, there was no difference in sensitization rates to milk, egg, or soy between the two groups. These findings on sensitization rates are similar to those reported in double-blind, placebo controlled trials of probiotics for eczema that examined sensitization to foods as a secondary endpoint.[32,34,35] In fact, one trial conducted in the Netherlands showed a trend toward an increase in sensitization rates to foods after 1 and 2 years of treatment with probiotics as compared with placebo.[35] Given these data, probiotics do not appear to be reliable methods for prevention or treatment of food allergy at this time.[44]

Food Antigen-expressing, Engineered Probiotic Bacteria

Although lactic acid bacteria (e.g. Lactobacillus and Lactococcus spp) have been used in some of the probiotic trials above, these microorganisms are also effective vehicles for antigen delivery via genetic engineering, and have been used in a wide array of immunologic and anti-infective strategies.[45] For use in the field of food allergy, these bacteria can be engineered to express various dietary antigens, and in theory, when administered to mucosal sites, these genetically engineered probiotic bacteria would then deliver the antigen to the mucosa in a Th1-promoting environment.

Although no human studies have been reported to date, there have been reports in murine models studying the administration of Lacotcoccus lactis engineered to express β-lactogolublin (β-lac) (milk) and ovalbumin (egg).[46–48] Although methods varied in these studies, each reported evidence to suggest that delivery of an adequate amount of antigen to mucosal sites via expression in engineered Lacotcoccus lactis could either treat or prevent sensitization to a target antigen via a shift in the immune response to a Th1 response or via CD4+ CD25+ regulatory T cells expressing TGF-β.

Cytokine-expressing, Engineered Probiotic Bacteria

Instead of engineering Lacotcoccus lactis to express an antigen, some researchers have engineered the bacteria to express regulatory or Th1 cytokines in order to promote tolerance upon administration.[49–52] For example, in one model, Lacotcoccus lactis transfected to secrete IL-10, administered via intragastric gavage prior to sensitization with β-lac, significantly diminished anaphylactic scores and decreased serum-specific IgE levels after challenge with β-lac.[50] There is also some evidence to suggest that treatment with two different strains of Lacotcoccus lactis, one expressing a Th1 cytokine (IL-12 in this case) and the other expressing an antigen of interest, could lead to a synergistic effect not obtained by administering either alone.[49]

Although these methods using engineered Lacotcoccus lactis to achieve tolerance provide an intriguing model with promising data, they have yet to be studied in humans and are far from clinical use.

Helminth Therapy

Treatment of inflammatory and allergic conditions with helminth therapy has been a novel approach that has recently garnered public attention. Many reports have shown a negative association of chronic helminth infection and allergic disease, thus forming one of the bases of the hygiene hypothesis.[53] Unfortunately, strong clinical data from rigorous trials on the use of helminth therapy for allergic diseases are sparse, and perhaps the best trial to date, using Trichuris suis ova for allergic rhinitis, did not show any clinical benefit.[54] Many proponents of helminth therapy still have hope that this therapy may be beneficial, and that immunomodulatory products of the worms, rather than simple infection, may provide the benefit.[55] In addition, given one report of the utility of helminth therapy in a murine model of food allergy and its use in inflammatory bowel disease (another immunologic deviation of the gut),[56,57] there is currently an ongoing trial examining the use of T. suis ova in peanut and tree nut allergy (Clinicaltrials.gov identifier: NCT01070498).

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