Q:

1/7/2014
I am interested in food allergy and food desensitization. I am looking for the effects of pre and probiotics in the induction of tolerance in these patients. Does it help desensitization?

A:

Thank you for your inquiry.

The topic of food desensitization is extremely broad, and I share with you two abstracts copied below which deal with this issue; namely that desensitization to food is not at this time recommended for the clinical practice of allergy. Although quite clearly studies have shown some success, for the reasons cited in two of the articles, at this time it is generally recommended that the use of this therapy be limited to academic centers with research interests in this topic.

The issue of the use of pre and probiotics for prevention of allergic disease is also quite broad and unsettled. It is far too complex to cover directly on our website, but there are excellent reviews as documented for you in the abstracts copied below.

I personally share the view of the World Allergy Organization Special Committee on Food Allergy and Nutrition as illustrated by the abstract by Fiocchi, et al., copied below; namely that, at this time, "published statements and scientific opinions disagree about the clinical use" of the administration of pre and probiotics.

To my knowledge, and according to a literary search, there have been no definitive studies looking at the effects of pre and probiotics in conjunction with food desensitization, but there are theoretical issues regarding their combined use in immunotherapy as discussed in the article by de Azevedo, et al., in the Journal of Applied Microbiology, abstracted below.

In summary:
1. Although pre and probiotics have been studied extensively, the results of these studies have been conflicting, and the clinical use of pre and probiotics remains controversial at this time.

2. In many studies, desensitization to food has been an effective way to treat a food allergy, but for a number of reasons, most experts dealing with this issue do not recommend the clinical use of desensitization to foods at the present time.

3. There, to my knowledge, is no definitive information on the combined use of food desensitization with pre and probiotics. There are theoretical considerations as discussed in the article by de Azevedo, et al. However, to my knowledge, at this time one cannot give an opinion as to whether the pairing of these therapies would offer any advantage.

Thank you again for your inquiry and we hope this response is helpful to you.

Curr Opin Allergy Clin Immunol. 2013 Jun;13(3):280-6. doi: 10.1097/ACI.0b013e328360ed66.
Probiotics and prebiotics in preventing food allergy and eczema.
Kuitunen M.
Author information
Helsinki University Central Hospital, Children's Hospital, Helsinki, Finland.
Abstract
Purpose of Review: To describe the current literature on clinical trials of probiotics for eczema and food allergy prevention in view of recent new approaches and long-term follow-ups.
Recent Findings: Attempting allergy prevention by probiotic administration has been most successful when assessing atopic eczema, the most prevalent allergic disease at an early age. More than half of the published studies demonstrate a decrease in eczema prevalence until 2 years, whereas the remaining studies fail to show an effect. Effects have been most consistent with combined prenatal and direct postnatal supplementation of the infant and appear strain-specific, with Lactobacillus rhamnosus most often showing an effect. Prenatal-only and postnatal-only studies often fail to show effects. Recent long-time follow-ups have shown promising but not consistent results. A very recent follow-up of a large well conducted cohort shows that long-term effects of eczema prevention persists until age 4 and prevention of respiratory allergies might also be possible.
Summary: Prevention of eczema with probiotics seem to work until age 2 years and extended effects until 4 years have been shown in high-risk for allergy cohorts. Effects are strain-specific, with L. rhamnosus showing the most consistent effects especially when combining pre and postnatal administration.

J Asthma. 2013 Dec 17. [Epub ahead of print]
The immunomodulatory effect of probiotics beyond atopy: an update.
Vitaliti G, Pavone P, Guglielmo F, Spataro G, Falsaperla R.
Author information
Pediatric Complex Operative Unit and Pediatric Acute and Emergency Unit, Policlinico-Vittorio-Emanuele Hospital, University of Catania , Catania , Italy.
Abstract
Abstract Background: In the past decades, the theory of "allergen avoidance" was considered the standard treatment for preventing the onset of allergic diseases. Recently, the concept of "immune tolerance" has replaced this old theory, and induction of tolerance by exposure is actually considered the appropriate method for preventing atopic diseases and other immunomediated pathologies. On the other hand, it is obvious that for public health reasons, abandoning current medical and hygienic practices is not desirable; therefore, safe alternatives, such as probiotics, have been suggested for providing necessary microbial stimulation.
Objective: The purpose of our review is to describe the immunomodulatory and anti-inflammatory properties of probiotics, reporting literature data on their effect when used for the treatment of immunomediated diseases. Materials and methods: Articles reporting the evidence on the use of probiotics in immunomediated diseases, such as atopy, cow's milk allergy and rheumatoid arthritis (RA), and in inflammatory diseases, such as inflammatory bowel diseases (IBDs), with or without statistical meta-analysis, were selected in three different search engines: (1) MEDLINE via PubMed interface, (2) Scopus and (3) Google Scholar for all articles published from inception to July 2013. Titles and abstracts of identified papers were screened by two independent reviewers to determine whether they met the eligibility criteria of interest to develop our review. Subsequently, full texts of the remaining articles were independently retrieved for eligibility by the two reviewers.
Results and Discussion: The recent literature is focusing its interest towards the immunologic properties of relatively harmless organisms, including lactobacilli and bifidobacteria, helminths and saprophytic mycobacteria that may skew immune responses towards immunoregulation by inducing Treg cells, rather than eliciting a pro-inflammatory immune response. For this reason, recent researches have been addressed on the use of probiotics to promote immunoregulation in atopic diseases, such as atopic/eczema dermatitis syndrome and food allergy, as well as in inflammatory-based diseases such as IBDs, RA and bronchial asthma.

Allergy Asthma Proc. 2010 Mar-Apr;31(2):103-11. doi: 10.2500/aap.2010.31.3313.
Any benefits of probiotics in allergic disorders?
Ozdemir O.
Author information
Division of Allergy/Immunology, Department of Pediatrics, Private SEMA Research and Training Hospital, Istanbul, Turkey.
Abstract
Development of the child's immune system tends to be directed toward a T-helper 2 (Th2) phenotype in infants. To prevent development of childhood allergic/atopic diseases, immature Th2-dominant neonatal responses must undergo environment-driven maturation via microbial contact in the early postnatal period. Lactic acid bacteria and bifidobacteria are found more commonly in the composition of the intestinal flora of nonallergic children. Epidemiological data also showed that atopic children have a different intestinal flora from healthy children. Probiotics are ingested live health-promoting microbes that can modify intestinal microbial populations in a way that benefits the host; and enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is insufficient but very promising evidence to recommend the addition of probiotics to foods for prevention and treatment of allergic diseases, especially atopic dermatitis. Clinical improvement especially in allergic rhinitis and IgE-sensitized (atopic) eczema has been reported too. Literature data for food allergy/hypersensitivity and asthma are not adequate for this guaranteed conclusion; however, clinical benefit of probiotic therapy depends on numerous factors, such as type of bacterium, dosing regimen, delivery method, and other underlying host factors, e.g., the age and diet of the host. The selection of the most beneficial probiotic strain, the dose, and the timing of supplementation still need to be determined. Accordingly, probiotics can not be recommended generally for primary prevention of atopic disease; and if probiotics are used in atopic infants/children for any reason, such as therapy or prevention, cautionary approach ought to be taken.

J Allergy Clin Immunol Pract. 2013 Jan;1(1):15-21. doi: 10.1016/j.jaip.2012.10.009. Epub 2012 Dec 27.
Peanut oral immunotherapy: is it ready for clinical practice?
Sampson HA.
Author information
Kurt Hirschhorn Professor of Pediatrics, Mount Sinai School of Medicine, New York, NY.
Abstract
The prevalence of peanut allergy in the United States and other Westernized countries has tripled in the past 15 years, now affecting more than 1% of the population. Strict peanut avoidance is the current standard of care. In the past decade, a number of small, largely uncontrolled clinical trials have suggested that oral immunotherapy (OIT) can effectively desensitize most children with peanut allergy. Some in the allergy community now feel that OIT is ready for clinical practice. In this review, the evidence base in the medical literature is examined. Although peanut OIT shows promise, the evidence currently available on its effectiveness, risk benefit, and potential long-term consequences is insufficient to support its use in clinical practice.

Allergy Asthma Proc. 2013 May-Jun;34(3):197-204. doi: 10.2500/aap.2013.34.3661.
Oral and sublingual peanut immunotherapy is not ready for general use.
Greenhawt MJ.
Author information
Department of Allergy and Clinical Immunology, University of Michigan Medical School, University of Michigan Health Systems, Ann Arbor, MI 48106, USA.
Abstract
Food oral immunotherapy (OIT) is an investigational peanut allergy treatment aimed to achieve specific oral tolerance induction. Allergic children are given titrated oral (or sublingual) doses of their allergen on a daily basis, unlike in subcutaneous immunotherapy (SCIT). OIT is theorized to cause a shift from a Th2 to a Th1 regulatory environment, reflected by increases in food-specific IgG4/IgE, and the production of FoxP3. Peanut OIT holds special promise because peanut allergy has an unfavorable natural history and is rarely outgrown. A high percentage of the participants experience symptoms during peanut OIT, including anaphylaxis, warranting epinephrine and/or discontinuation of therapy. This is a concerning fact given that the studies have mostly targeted only older children, with less historical reactivity for enrollment. The handful of peanut OIT studies have shown that some participants can be desensitized to peanut, but none have shown that long-term tolerance can be reestablished. Factors predictive of which patients are most likely to succeed and become desensitized through OIT are unknown. Some private practices have begun offering peanut OIT as a therapy. Such practice is potentially dangerous given the safety and efficacy of OIT in randomized controlled clinical trials is still not well established. Therefore, until further investigation emerges that conclusively demonstrates OIT is safe, intermediate and long-term outcomes are better established, the number of participants that experience symptoms is reduced, and proof of concept established in patients of all ages, (irrespective of past reaction severity), OIT is not ready for use in the general allergy practice.

J Appl Microbiol. 2013 Aug;115(2):319-33. doi: 10.1111/jam.12174. Epub 2013 Mar 13.
Immunotherapy of allergic diseases using probiotics or recombinant probiotics.
de Azevedo MS, Innocentin S, Dorella FA, Rocha CS, Mariat D, Pontes DS, Miyoshi A, Azevedo V, Langella P, Chatel JM.
Author information
Laboratório de Genética Celular e Molecular, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB/UFMG), Belo Horizonte, MG, Brazil.
Abstract
Allergic diseases affect up to 30% of the western population, and their prevalence is increasing. Probiotics are able to modulate the mucosal immune response, and clinical trials demonstrated that specific strains, especially lactic acid bacteria (LAB) ones, reduce allergic symptoms. Moreover, the use of recombinant probiotics has been evaluated as possible strategies for the immunotherapy of allergic diseases. The production and delivery of allergens by recombinant LAB in concert with their ability to induce a Th1-type immune response have been shown to be a promising mucosal vaccination strategy in mouse model. The aim of this article is to review the applications of probiotics in allergy immunotherapy with a special focus on recombinant LAB delivering proteins or DNA.

World Allergy Organ J. 2012 Nov;5(11):148-67. doi: 10.1097/WOX.0b013e3182784ee0.
Clinical Use of Probiotics in Pediatric Allergy (CUPPA): A World Allergy Organization Position Paper.
Fiocchi A, Burks W, Bahna SL, Bielory L, Boyle RJ, Cocco R, Dreborg S, Goodman R, Kuitunen M, Haahtela T, Heine RG, Lack G, Osborn DA, Sampson H, Tannock GW, Lee BW; WAO Special Committee on Food Allergy and Nutrition.
Author information
1Department of Pediatrics - Division of Allergy - Pediatric Hospital Bambino Gesù - Rome, Vatican City 2Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA 3Department of Pediatrics and Medicine, Section of Allergy and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 4Department of Medicine, University of Medicine and Dentistry of New Jersey Medical School, Newark, NJ 5Department of Paediatrics, Imperial College London, London, United Kingdom 6Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil 7Department of Pediatric Allergology, Women's and Children's Health, University of Uppsala, Uppsala, Sweden 8Department of Food Science & Technology University of Nebraska, Lincoln, NE, USA 9Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland 10Department of Allergy and Immunology, Royal Children's Hospital, University of Melbourne, Murdoch Childrens Research Institute, Melbourne, Australia 11King's College London, Asthma-UK Centre in Allergic Mechanisms of Asthma, Department of Paediatric Allergy, St Thomas' Hospital, London, United Kingdom 12Sydney Medical School, University of Sydney, New South Wales, Australia 13Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY 14Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand 15Department of Paediatrics, National University of Singapore, Singapore.
Abstract
Background: Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.
Objective: A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.
Methods: A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.
Results: Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.
Conclusions: Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology