Several human trials, as well as, numerous animal and in vitro studies suggest a beneficial effect of probiotics in allergic diseases. The therapeutic and preventive role of probiotics in atopic dermatitis has been extensively studied.

The prevention of allergic diseases relies heavily on preventing sensitization to an offending allergen. Enomoto and colleagues investigated the association of consumption of fermented dairy products and the development of allergy and allergic sensitization in Japanese students as reflected on serum levels of total IgE values, specific IgE to house dust mite and Japanese cedar pollen. The report demonstrated a significant reduction in allergy development among the students consuming fermented milk in comparison with students who did not consume fermented products25.

The effect of probiotics on preventing atopic dermatitis has been demonstrated in randomized studies from Finland where Lactobacillus GG or placebo was given to pregnant mothers with a strong family history of eczema, allergic rhinitis or asthma, and to their infants for the first six months after delivery. The frequency of developing atopic dermatitis in the offspring was significantly reduced by 2, 4, and 7 years 262728, by 50%, 44%, and 36% respectively.

Similar studies have yielded comparable results. The use of the probiotic E-coli in the early postnatal period decreased the incidence of serum specific IgE allergies at 10 and 20 years of age in a long-term prospective study 2930. Other studies could only relate probiotic benefits to a certain subset of dermatitis patients. The incidence of IgE-associated dermatitis, rather than other types of atopic dermatitis, was decreased after the oral consumption of probiotics, namely L. reuteri or a mixture of four probiotic bacteria and prebiotics 3132. However, Taylor et al could not confirm such effects in a randomized placebo-controlled double-blind study. L. acidophilus did not decrease the risk of developing allergy in a large number of infants3334. There were two major differences between Taylor^Ds study and the others. The type of probiotic product was different as well as the timing of the introduction of the probiotic, Taylor et al administered the probiotic supplement postnatally, while other studies administered probiotics before and after birth. Prenatal supplementation may prove to be crucial for the preventive benefit of probiotics in this disorder.

Prebiotic oligosaccharides have also been shown to reduce the incidence of atopic dermatitis when given to infants at risk for atopy during the first six months of age35. No comparisons made to probiotics and have not been used prenatally.

A recent Cochrane review meta-analysis found a significant reduction in the likelihood of developing infant eczema with the use of probiotics. The meta-analysis described five studies enrolling 1477 infants. However, the authors found significant heterogeneity and with further focused on children with dermatitis that have positive skin prick test or specific IgE sensitization, there were no significant benefits noted with probiotics. The authors concluded that there was no current evidence to support the administration of probiotics to prevent eczema and recommended further studies to determine reproducibility36.

In general, the role for probiotics in the prevention of atopic dermatitis (table 1) awaits future studies.

Once allergic diseases develop, one goal of therapy is to control the patient's clinical symptoms. Probiotics may help to decrease the severity of atopic dermatitis and food allergy. Most clinical studies have targeted pediatric patients (table 2).

In 1997, the first published study in this area 37 examined the effect of Lactobacillus GG in mild atopic eczema in a modest number of infants. After four weeks, SCORAD scores dropped from 26 to 15, while the control group only changed from 21 to 19. However, one month after the probiotic was discontinued, both groups had comparable SCORADs. Therefore, in this particular study, the effect of the probiotic was short lived.

The same group of investigators subsequently published two additional studies. One study, published in 200038, compared Lactobacillus GG, or Bifidobacterium lactis Bb-1 2 to placebo. After two months SCORAD scores decreased from a baseline of 16 to 1, 0, and 13.4 respectively. However, after 6 months, the median SCORAD was zero (0-6.6) in all groups, suggesting that the probiotic effect is limited to rapid initiation of improvement in mild disease. The other study underscored the importance of viability 39. While live probiotic administration resulted in statistically significant improvement of scores, the use of heat-inactivated Lactobacillus GG was associated with adverse gastrointestinal symptoms and further study enrollment was thus halted.

Another study by Kirjavainen et al suggested that Bifidobacterium lactis Bb12 modifies gut microflora to alleviate early onset atopic eczema7. A randomized, but not placebo-controlled study suggested that synbiotics and prebiotics significantly improve atopic dermatitis in older children 40.

The largest study (n = 230) to date, compared the effects of Lactobacillus GG, a probiotic mix, or placebo41. There was no difference between the groups after 4 weeks of therapy, or4 weeks after study supplement was discontinued. However, infants receiving Lactobacillus GG who had specific IgE sensitization had a greater reduction in SCORAD when compared to the placebo group (-26.1 versus -19.8, p = 0.036). Furthermore, a reduction of TNF-alpha and an increase in fecal IgA levels were noted 42. Two other studies demonstrated comparable results. A study by Rosenfeldt et al. from Denmark used lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460) in older children (average age 5.2 years), and statistically significant improvement in SCORAD was only seen in a subset of children with positive skin prick test and elevated IgE levels 43. Another study by Sistek et al. showed efficacy of the probiotic Lactobacillus rhamnosus and Bifidobacteria lactis in food-sensitized children44. Those three studies taken together reveal that probiotics were not effective for all children with atopic dermatitis but rather in the subset of IgE sensitized children.

However, a study from the Netherlands by Brouwer et al.45 and another study from Germany by Folster-Holst et al.46 showed no effect of Lactobacillus rhamnosus or Lactobacillus GG in infants with atopic dermatitis regardless of their IgE sensitization status.

In 2005, Weston et al.47 from Australia published their experience with using Lactobacillus fermentum VRI-003 PCC for 8 weeks in 53 infants with atopic dermatitis. After 16 weeks the probiotic group had significant reduction of SCORAD scores (p = 0.03) while the placebo group did not (p = 0.83). However, while the change in SCORAD scores from baseline in the probiotic group was significant, the difference between the probiotic and placebo group did not quite reach statistical significance (p = 0.06) by the 16^th week.

As pointed out by Passeron and Lacour, in their letter to the editor48, children receiving placebo treatment in many of these studies significantly improved within a much shorter than expected time. Cellulose and maltose dextran were used as placebo, which could have a prebiotic effect thus explaining the improvement seen in the placebo group. To further examine this effect, the same investigators compared the effects of prebiotics and probiotics (synbiotics) versus prebiotics alone and concluded that both groups had a significant reduction in the SCORAD scores after 3 months40.

The most recent randomized trial was designed to investigate the therapeutic benefit of Lactobacillus rhamnosus GG (LGG) in infants with atopic dermatitis. Infants 3-12 months of age with mild-to-moderate atopic dermatitis were randomized to receive LGG or placebo as a food supplement for 12 weeks. Fifty-four infants received LGG and 48 infants received placebo. Symptoms improved overtime after 4, 8, and 12 weeks, without any group being statistically different 49.

A recent meta-analysis suggested that probiotics may benefit children and infants with the disorder 50. The meta-analysis identified ten randomized, controlled trials. A significant overall benefit was demonstrated after the use of probiotics, resulting in a reduction of the dermatitis scores (SCORAD) compared to placebo. Lactobacillus GG appeared to be more effective than other probiotic preparations and children with more severe disease were more likely to benefit from the use of probiotics. Another recent meta-analysis did not show a therapeutic difference among children receiving probiotics 51. However, this analysis excluded six of the ten studies published, making the validity of the report questionable.

Other studies have examined the effect of probiotic consumption on sensitization to several allergens (e.g. peanut, hen's egg, soy, wheat, milk, cat, dog), as determined by specific IgE production or skin prick test reaction (SPT). The authors could not find a difference before and after the treatment222645.

Taken together, some of these studies show a slight benefit over placebo for the treatment of atopic dermatitis. However, several of the studies show no benefit.

A small number of studies exist that try to address the efficacy of probiotic supplementation in the treatment or prevention of asthma. Such studies have heavily focused on the treatment rather than prevention of asthma. Perhaps the largest and the most recent trial was conducted by Giovannini and colleagues using fermented milk containing Lactobacillus casei and studying its effect on the number of episodes of asthma and allergic rhinitis52. One hundred and eighty seven children, between two and five years of age, were included in the study. At the end of the twelve-month trial period the investigators found no statistical difference between intervention and control groups of asthmatic children. However, the number of rhinitis episodes was lower in the probiotic group leading the authors to conclude that Lactobacillus casei may benefit children with allergic rhinitis but not asthmatic children.

One randomized placebo-controlled crossover study examined the effect of yogurt containing S. thermophilus and Lactobacillus bulgaricus when given with or without Lactobacillus acidophilus to adolescents and adults with asthma who were sensitized to inhalant allergens. There was no difference in clinical parameters of asthma or laboratory markers of inflammation53. One concern with this experimental design arises from the fact that the placebo group received yogurt mixed with bacteria that have probiotic properties. At any rate, neither the active group nor placebo had any improvement in lung function.

The efficacy of probiotics in asthma as a preventive measure has not been evaluated and may be worthwhile studying. However, to date there is no evidence to justify the use of probiotics for treatment or prevention of asthma.

Reports on the efficacy of probiotics in treating allergic rhinitis are conflicting. Some studies suggest efficacy such as the study by Wang and colleagues, where Lactobacillus paracasei-33 was given for 30 days to 80 children with perennial rhinoconjunctivitis. The quality of life questionnaire scores significantly improved relative to placebo54. A Japanese study demonstrated that intake of Bifidobacterium lon gum BB536 as a yogurt supplement is effective in relieving symptoms of Japanese cedar pollinosis5556. Furthermore, a Finnish study suggested that fermented milk prepared with Lactobacillus gasseri TMC0356 could alter serum IgE concentration through a Th1 immune response in subjects with perennial allergic rhinitis57. Others reported that the ingestion of B. longum reduced ocular and nasal symptoms as well as need for medication, again in Japanese cedar pollinosis 55565859. With regard to house dust mite allergy, the use of probiotics resulted in a reduction of symptoms in children and adults with allergic rhinitis 6061. In a recent study by Giovannini 52, L. casei DN-1 14 001 reduced the number of rhinitis episodes in sixty-four pre-school children with allergic rhinitis. Other studies did not show benefit, for example, patients who were allergic to birch pollen and apple food that were treated with L. rhamnosus GG during the birch-pollen season, had no reduction of symptom score, nor of sensitization to birch pollen and apple after Lactobacillus rhamnosus supplementation 62 and L. casei strain Shirota did not reduce allergic symptoms of Japanese cedar pollen allergy 63.