The Anti-allergic Effects of Specific Probiotics
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional
Phase: Phase 1

Summary: 
      We hypothesize that specifically selected probiotics can alleviate symptoms of allergy in
      lactose tolerant individuals. Two strains of probiotics, Lactobacillus rhamnosus GR-1, and
      Bifidobacterium adolescentis 7007-05 will be used to create a yogurt product. Additionally a
      non-probiotic yogurt product will also be made as a placebo. Allergy sufferers will be asked
      to consume one of the two types of yogurts (blinded) for two months. During the two months
      there will be 3 sampling days, for blood samples and nasal lavage samples. Additionally Mini
      Rhinoconjunctivitis Quality of Life Questionnaires will be filled out weekly over the two
      months. After the two months of perceived responses as well sample analysis we should have a
      better idea of how these specific probiotic effect the immune system and allergies.
    

Detailed description: 
      Probiotics are "live microorganisms which when administered in adequate amounts confer a
      health benefit on the host". Many studies have been performed which indicate that probiotics
      can temporarily modify the composition of gut microbiota, and potentially these can reduce
      susceptibility to allergy (Noverr & Huffnagle, 2005) (Tannock et al. 2000), leading to health
      benefits for the host. Numerous studies show that these benefits include ones primed through
      the immune response of the host.

      Animals maintained free of microorganisms have drastic abnormalities in their immune
      response. These germ-free animals have altered Peyer's Patches, reduced levels of IgA
      associated with increased risk for gastrointestinal infections, and they are unable to
      develop oral tolerance to ingested antigens (Moreau et al. 1988). When these animals are
      later colonized by normal intestinal bacteria, they overcome their past deficiencies, and
      have a restored ability for oral tolerance. This allows for the blockade of IgE production
      which is a key factor in allergic disease (Moreau et. al 1988).

      Studies on inflammatory bowel disease patients have shown that certain probiotics can
      actually reduce inflammation and diminish disease (Bruzzese et al. 2004) (Baroja et al.
      submitted). The former study investigated 75 children, while our study (Baroja) showed down
      regulation of inflammation in 8/20 inflammatory bowel diseased patients. Allergic disease is
      almost non-existent in underdeveloped countries where, interestingly, fermented foods are
      consumed regularly. This differs considerably from the numerous allergies and lack of
      fermented food intake in the Western World. Investigators hypothesize that the human gut
      ecosystem has evolved to require daily intake of lactic acid bacteria (Molin 2001), and these
      bacteria maintain immunological regulation which protects against allergic sensitization and
      development of allergic disease.

      Recent studies have shown that probiotics do have a significant influence on allergic
      reactions. The consumption of Lactobacillus rhamnosus GG by pregnant women lowered the
      occurrence of babies born with atopic dermatitis compared to those births from women who had
      not consumed the probiotic (Kalliomaki et al. 2001). Another study on 27 infants suffering
      from atopic eczema, showed that probiotic-supplemented formula decreased the severity of the
      condition (Isolauri et al 2000). The efficacy of probiotics in treating allergy has been
      further shown with Bifidobacterium longum BB536 in which it relieved Japanese cedar tree
      pollinosis, probably through the modulation of Th2-skewed immune response (Xiao et al. 2006).
      Another Japanese study showed that a synbiotic L. casei subsp. casei with dextran was an
      effective supplement for the prevention and treatment of allergic reactions cedar pollen
      (Ogawa et al. 2006). Not all studies have shown benefits, and one performed in teenagers and
      young adults allergic to birch pollen and apple food, showed no effect on intermittent
      symptoms of atopic allergy and/or mild asthma. We have now isolated strains of bifidobacteria
      from the stool of subjects with no history of any allergy, and these along with two
      lactobacilli probiotics have shown strong anti-allergy potential in vitro. In short, there is
      evidence to indicate that studies are worthwhile using food based probiotics, if not to
      completely prevent allergies, but to contribute towards their alleviation.

      Objective 1. We will examine the cell types in nasal cavity with the expectation that this
      will shift as the probiotics are consumed, with a decrease in number of eosinophils,
      characteristic of late-phase allergic inflammatory symptoms, as the study progresses, and a
      corresponding decrease in neutrophils.

      Objective 2. We will characterize the subject's sensitivities to inhalant seasonal and
      potentially year-round allergens. Routine RAST tests will be performed at the beginning of
      the study to test sensitivity towards mixed grasses, mixed trees, mixed weeds, mixed molds,
      ragweed, house dust, cat dander and dog dander. From this we will be able to differentiate
      subjects who are highly susceptible to allergy and those moderately susceptible. At the end
      of the trial we will perform further RAST tests using ragweed and mixed grass allergens, with
      the anticipation that the probiotic treatment with anti-allergic strains will decrease the
      subject's sensitivity to those particular allergens, while those receiving regular yogurt
      will have no effect.

      Objective 3. We will identify changes in serum cytokine levels that would indicate a shift
      from an inflammatory state to one of reduced inflammation. We anticipate that the presence of
      inflammatory cytokines, IL-5, IL-4 and IL-13 will be decreased as the subject's intestinal
      flora is boosted by the anti-allergic probiotics; likewise, the presence of anti-inflammatory
      cytokines, IL-10, TGFβ2, IFN-γ will be increased by the treatment. This shift in cytokine
      production should be reflected in reduced allergic symptoms. In addition, Affymetrix Human
      Genome U133 Plus 2.0 Arrays will be performed on selected blood samples to characterize
      immunological signal transduction pathways activated by the probiotic bacteria.

      Objective 4. We will characterize the perceived effects of anti-allergic strains of
      probiotics using a questionnaire. Subjects will self-administer validated Mini
      Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ)© (Juniper et al., 2000) on day 0
      and weekly during the study period. The questionnaire includes 14 questions in five domains:
      activity limitations, practical problems and nose symptoms, eye symptoms and other symptoms.
      The questions are answered on scale 0-6 (from not troubled to extremely troubled) depending
      how troubled the subjects have been due to their nose/eye symptoms during the past week.
      Possible lung symptoms (cough, dyspnoea and wheezing) will be recorded separately using the
      same scale. This perceived effect may actually be the single most important outcome to our
      study. If the samples actually do show a decrease in inflammatory cytokines etc. but the
      subject does not perceive any changes to their allergy symptoms, then the probiotics cannot
      be stated to have affected the allergic response. We hope that all shifts in cytokine and
      cellular levels towards the anti-inflammatory state are reflected in the subject's awareness
      of decreased allergy symptoms.

      At the end of this study we hope to know whether or not regular and probiotic yogurts have
      the potential to alleviate symptoms of allergic rhinitis, as well as down regulate the
      inflammatory processes in humans. It is anticipated that at least one of the yogurts will
      show promise in this regard. However, even a negative result would be informative, as the
      experiments will show us how consumers respond physiologically to different fermented food.
    

Intervention name(s): Probiotic or placebo yogurt consumed daily; Mini Rhinoconjunctivitis Quality of Life Questionnaire; Blood sample; Nasal lavage
Intervention type(s): Behavioral; Device; Procedure; Procedure
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Supportive Care
Keywords: grass allergies,; ragweed allergies,; probiotics, lactobacillus,; bifidobacterium,; functional foods,; yogurt,; inflammatory cytokines