Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data


Ö. Özdemir, SEMA Research and Training Hospital, 34844 Dragos, Maltepe, Istanbul, Turkey.


Epidemiological data show that allergic children have a different intestinal flora from healthy children with higher levels of Clostridia and lower levels of Bifidobacteria. Nonetheless, Bifidobacteria and Lactobacilli are found more commonly in the composition of the intestinal flora of non-allergic children. Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host and they are represented mainly by Lactobacilli. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is also very promising evidence to recommend the addition of probiotics to foods for the prevention and treatment of allergic diseases. Clinical improvement, especially in allergic rhinitis and immunoglobulin (Ig)E-sensitized (atopic) eczema, has been reported in most of the published studies. However, clinical benefit of probiotic therapy depends upon 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. Selection of the most beneficial probiotic strain, the dose and the timing of supplementation still need to be determined. This review helps understanding of the role of probiotics in various allergic diseases, explaining laboratory and clinical data in light of recent literature.


Development of the child's immune system tends to be directed towards a T helper type 2 (Th2) phenotype in infants, whereas postnatal maturation is associated with gradual inhibition of Th2 and increasing Th1 affinity [1]. Thus, immature Th2-dominant neonatal responses must undergo environment-driven maturation via microbial contact in the early postnatal period to prevent the development of childhood allergic diseases. Otherwise, at an early age the infant's immune system results in subsequent polarization towards a Th2 phenotype during postnatal maturation. Nowadays, the increased use of anti-microbial medication, the consumption of sterile food and reduced family size that result in lower rates of infection during childhood also reduce early contact to microbes. Consequentially, the present increase in allergic diseases seen in the industrialized countries has been attributed, among several other phenomena, to a relative lack of microbial stimulation of the infantile gut immune system and the exaggerated hygiene of the typical western lifestyle during early childhood. This is known as the ‘hygiene hypothesis’[2].

The newborn is first colonized by microbes at birth. The colonization of the gut that begins promptly after birth is affected by mode of delivery, early feeding strategies and the hygienic conditions around the child (the early environment). The colonizing bacteria originate mainly from the mother's gut and vaginal tract [3]. For instance, children born by caesarean section are colonized with Bifidobacteria (Bfdba) and Lactobacilli (Lctb) later than vaginally delivered children, and are shown to have more frequent respiratory allergies [4]. After delivery, breast feeding continues to enhance the original inoculum by the introduction of specific lactic acid bacteria (Lab), Bfdba and bacteria from the mother's skin, all of which enable the infant gut microbiota that is dominated by Bfdba. Breast milk also contains plentiful indigestible oligosaccharides, which pass through the whole intestine and promote the growth and activity of commensal bacteria, composed mainly of Bfdba [5]. These bacteria set the basis for gut microbiota development and modulation, along with environmental exposures such as antibiotic administration.

The greatest differences between breast-fed and formula-fed infants appear to be in Lab and Bfdba colonization. Usually, Bfdba appear after birth and, within a week, are reported as the dominant bacterial group, with Bifidobacterium (Bfdbm) infantis/longum/breve being the most common species in breast-fed infants [6]. In addition, Lactobacillus (Lctbs) acidophilus is the most common Lctb in the faeces of breast-fed infants. Formula-fed infants, on the other hand, tend to have a flora that is more complex, consisting mainly of Coliforms and Bacteroides, with a significantly lower prevalence of Bfdba [7]. After weaning, the microflora of children begins to resemble that of adults, with increased Bacteroides, Veillonella and Fusobacterium [8].

Epidemiological data have shown that atopic children have a different intestinal flora from that of healthy children, with higher levels of Clostridia and lower levels of Bfdba. Furthermore, other studies have also shown that early colonization with potentially more pathogenic bacteria such as Clostridium difficile and Staphylococcus aureus is more likely to occur in children who go on to develop allergy. In contrast, Lab and Bfdba are found more commonly in the composition of the intestinal flora of non-allergic children. The enhanced presence of these probiotic bacteria in the intestinal microbiota seems to correlate with protection against atopy [9,10]. Based on these data, ‘harmless’ microbial agents that are probiotics are being tested currently for their efficacy in the prevention and therapy of allergy in infants [11–13]. The aims of this review are to define probiotic properties comprehensively and to characterize current knowledge of probiotics, including the key mechanisms of probiotic effects and their preventative/therapeutic role in various allergic diseases.

What are probiotics?

The year 2009 marks the 102nd year since Eli Metchnikoff suggested that the consumption of Lab may benefit the human host's immune system [11]. However, not until the mid-1960s did the term ‘probiotic’ become the trend. Probiotics means ‘for life’ and are defined by the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations as ‘live microorganisms which, when administered in adequate amounts as part of food, confer a beneficial health effect by producing gut microflora on the host’. These probiotics are represented mainly by Lab [12]. Put simply, probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host.

Characteristics of probiotics

There are several generally accepted characteristics that define probiotic bacteria. Probiotics:

  • • are microbial organisms;
  • • remain viable and stable after culture, manipulation and storage before utilization;
  • • survive gastric, biliary and pancreatic digestion;
  • • are able to induce a host response once they enter the intestinal microbial ecosystem; and
  • • yield a functional or clinical benefit to the host when consumed [10–13].

What is yogurt (yoğurt)?

Fermented foods, particularly dairy products such as yogurt, have been consumed for centuries. In particular, Lab members of the genus Lctb, Bfdbm and Streptococcus are the most widely used in the food supply. Yogurt contains viable bacteria culture including Streptococcus thermophilus and Lctbs delbrueckii sp. bulgaricus. Although these cultures clearly fulfill the current concept of probiotics, only a small number of these bacteria have been studied. However, some have been shown specifically to have a probiotic effect [14].

Probiotics and their role in allergic diseases

Current laboratory and clinical data regarding the possibility of the role of probiotics on preventing the development of allergic diseases, sensitization or both are still contradictory, and are somewhat insufficient to recommend strongly the use of probiotics. To improve upon the knowledge of probiotic bacteria, this review explains laboratory data from experimental models (mainly murine) and clinical (mainly human) data. Discussed first are the supposed mechanisms of probiotics' effects, and then their role in various allergic diseases with recent laboratory and clinical studies collected from Pubmed/Medline.

Experimental models describing supposed mechanisms of the effect of probiotics

The mechanisms of action of probiotics are multi-faceted, and each probiotic may have specific functions affecting the host [15]. Hypothesized mechanisms that reduce the risk of allergic diseases and help in therapy are discussed in detail below. The diverse effects of different probiotic strains in mechanisms of allergic disorders are shown in Table 1.

Table 1.  Various effects of different probiotic strains in mechanisms of allergic disorders are shown from experimental models referred to in the text.
ReferencesProbiotic strainEffect of probioticOutcome
  1. ↑: Increase in symptoms or negative effect; ↓: decrease in symptoms or positive effect; ↔: no change in symptoms or no effect; Bfdbm: Bifidobacterium; Lctbs: Lactobacillus; LGG: Lctbs rhamnosus GG; IgA: immunoglobulin A; Th1: T helper type 1; IL: interleukin; TGF: transforming growth factor; IFN: interferon.

  Maturing gut barrier 
Sudo et al.[16]BfdbmOral tolerance
Isolauri et al.[18]LGGFaecal IgA levels
Isolauri et al.[18]Lctbs rhamnosus GG (LGG)Gut-stabilizing effect
Malin et al.[20]LGGGut defence
Kaila et al.[22]LctbsIntestinal permeability
  Ovalbumin-induced food allergy 
Kim et al.[27]Bfdbm lactis/bifidum; Lctbs acidophilusTh1/Th2 balance
Torii et al.[42]Bfdbm bifidum; Lctbs acidophilusTGF-β production
  Th1 cytokines 
Maassen et al.[26]Lctbs reuteriTh1/Th2 balance
  Th2 cytokines 
Niers et al.[25]Bfdbm bifidum/infantis; Lctbs lactisTh1/Th2 balance
Takahashi [28]Bfdbm longumTh1/Th2 balance
  IL-10 production 
Niers et al.[25]Bfdbm bifidum/infantis; Lctbs lactisTh1/Th2 balance
Maassen et al.[26]Lctbs caseiTh1/Th2 balance
Kim et al.[27]Bfdbm lactis/bifidum; Lctbs acidophilusTh1/Th2 balance
Sistek et al.[31]Lctbs rhamnosus GG (LGG)Th1/Th2 balance
Kruisselbrink et al.[33]Lactobacillus plantarumTh1/Th2 balance
Hart et al.[36]Bfdbm bifidumTh1/Th2 balance
Smits et al.[38]Lctbs reuteri/caseiPrime monocyte-derived dendritic cell
  IL-4 production 
Maassen et al.[26]Lctbs caseiTh1/Th2 balance
Kim et al.[27]Bfdbm lactis/bifidum; Lctbs acidophilusTh1/Th2 balance
Mohamadzadeh et al.[35]Bfdbm bifidumMost potent polarizer of dendritic cells
Kim et al.[27]Bfdbm lactis/bifidum; Lctbs acidophilusTh1/Th2 balance
Mohamadzadeh et al.[35]Bfdbm bifidumMost potent polarizer of dendritic cells
  IgE production 
Kim et al.[27]Bfdbm lactis/bifidum; Lctbs acidophilusImmunomodulation
Takahashi et al.[28]Bfdbm longumImmunomodulation
Gill et al.[29]Bfdbm lactis Bb-12Immunomodulation
Borchers et al.[30]LGGImmunomodulation
Torii et al.[42]Bfdbm bifidum; Lctbs acidophilusImmunomodulation
  Serum inflammatory parameters 
Maassen et al.[26]Lctbs reuteriImmunomodulation
Sistek et al.[31]Lctbs rhamnosus GG (LGG)Immunomodulation
  Development of tolerogenic dendritic cells 
Niers et al.[34]BfdbmPrime neonatal dendritic cells
Mohamadzadeh et al.[35]Bfdbm bifidumMost potent polarizer
Braat et al.[37]Lctbs rhamnosusModulates dendritic cell function
Smits et al.[38]Lctbs reuteri/caseiPrime monocyte-derived dendritic cells
  Toll-like receptor (TLR) stimulation 
Hoarau et al.[39]Bfdbm bifidum/infantis; Lctbs salivariusActivate TLR-2
Forsythe et al.[40]Lctbs reuteriActivate TLR-9
  Regulatory T cell production 
Smits et al.[38]Lctbs reuteri/caseiPrime monocyte-derived dendritic cells
Torii et al.[42]Bfdbm bifidum; Lctbs acidophilusTGF-β production
  T cell hyporesponsiveness 
Kruisselbrink et al.[33]Lactobacillus plantarumInhibits specific T cell responses
Braat et al.[37]Lctbs rhamnosusModulates dendritic cell function

Maturing gut barrier.  Recent data indicate that the commensal intestinal microbiota represents a major modulator of intestinal homeostasis. Dysregulation of the symbiotic interaction between intestinal microbiota and the mucosa may result in a pathological condition with potential clinical repercussions. For instance, it is shown that mice reared in germ-free conditions have an underdeveloped immune system and have no oral tolerance. In contrast, pathogen-free mice are capable of reconstituting the bacterial flora with Bfdba and tolerance development [16].

In addition to providing maturational signals for the gut-associated lymphoid tissue, probiotics balance the generation of pro- and anti-inflammatory cytokines in the gut. After probiotic consumption, decrease in faecal α-1 anti-trypsin, serum tumour necrosis factor (TNF)-α and changes in transforming growth factor (TGF)-β and other cytokines point to down-regulation of inflammatory mediators [17]. For instance, after a challenge study in infants allergic to cow's milk, faecal immunoglobulin (Ig)A levels were detected to be higher and TNF-α levels were lower in the Lctbs rhamnosus GG (LGG) applied group compared to the placebo [18]. Additionally, probiotic bacteria may counteract the inflammatory process by stabilizing the gut microbial environment and the permeability barrier of the intestine, and by enhancing the degradation of enteral antigens and altering their immunogenicity [19]. This gut-stabilizing probiotic effect could be explained specifically by probiotic improvement of the immunological intestinal barrier through intestinal IgA responses [20,21]. Consistent with these explanations, in children with food allergies probiotics are shown to reverse increased intestinal permeability and to enhance frequently defective IgA responses [22].

Immunomodulation: cytokines, Th1/Th2 balance, IgE production and serum inflammatory parameters.  In addition to maturing gut barrier, certain strains of Lctb and Bfdba modulate the production of cytokines by monocytes and lymphocytes, and may divert the immune system in a regulatory or tolerant mode [23]. Nonetheless, there are still some studies showing no significant effects of probiotics on either Th1 or Th2 cell responses to allergens. Although the cytokine stimulation profiles of different probiotic strains vary, the strains isolated from healthy infants stimulate mainly non-inflammatory cytokines [24]. Therefore, it seems that changes in the cytokine profile induced by probiotics may be probiotic strain- or site-specific and dependent upon the experimental system used.

Several studies have shown the immunomodulatory effects of probiotic bacteria. In one study, Bfdbm bifidum/infantis and Lctbs lactis reduced Th2 cytokines and acted as potent inducers of interleukin (IL)-10 production in different peripheral blood mononuclear cell cultures [25]. In another study, eight common Lctbs strains were studied with respect to induction of cytokines by the murine gut mucosa in response to a parenterally administered antigen. Lctbs reuteri induced proinflammatory and Th1 cytokines; however, Lctbs casei tended to induce IL-10/IL-4 [26]. In a mouse model the effect of oral probiotics administration, including Bfdbm lactis/bifidum and Lctbs acidophilus, was studied in mice with ovalbumin (OVA)-induced food allergy. The mice probiotics-treated suppressed production of the OVA-specific IgE, IgG1 and IgA. Additionally, the level of IL-4 was significantly lower, and the levels of interferon (IFN)-γ and IL-10 were significantly higher in the mice treated with probiotics than those in the non-treated mice [27]. Another murine model showed that oral administration of an immunostimulatory DNA sequence from Bfdbm longum suppressed Th2 immune responses in mice and inhibited IgE production in vitro[28]. A final study showed that the administration of either Bfdbm lactis Bb-12 or LGG also suppressed antigen-specific IgE production [29,30].

Oral administration of LGG resulted in elevated IL-10 concentrations in atopic children, indicating that specific probiotics may have anti-inflammatory effects in vivo and possibly also enhancing regulatory or tolerance-inducing mechanisms. Probiotics also increased Th1 cytokines and inhibited allergen-induced IgE and Th2 cytokines in some atopic children [31,32]. Conversely, in some children receiving probiotics, reduced IL-10 responsiveness to house dust mites allergens was observed [33].

Development of tolerogenic dendritic cells.  Selected species of the Bfdbm genus were demonstrated to prime in vitro-cultured neonatal dendritic cells (DCs) to polarize T cell responses and may therefore be used as candidates in primary prevention of allergic diseases [34]. Bfdbm bifidum was found to be the most potent polarizer of in vitro-cultured DCs to drive Th1 cell responses involving increased IFN-γ-producing T cells, concomitant with a reduction of IL-4-producing T cells [35]. In addition, T cells stimulated by Bfdbm bifidum matured DCs as producers of more IL-10 [36]. Moreover, Lctbs rhamnosus, a member of another genus of probiotic bacteria, modulates DC function to induce a novel form of T cell hyporesponsiveness [37]. Lctbs reuteri/casei have also been shown to prime monocyte-derived DCs through the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) to drive the development of regulatory T cells (Tregs) [38]. These Tregs produce increased levels of IL-10 and are capable of inhibiting the proliferation of bystander T cells. This study suggests that the targeting of DC-SIGN by certain probiotic bacteria might explain their beneficial effect in the treatment of a number of inflammatory diseases, including atopic dermatitis (AD).

Toll-like receptor (TLR) stimulation.  Some researchers hypothesized that the protection offered by probiotics against allergic diseases is based on stimulation of TLRs, which produce mediators such as IL-6; these induce further IgA differentiation from naive B cells. Consistently, Lab species such as Bfdbm bifidum/infantis and Lctbs salivarius were shown to be capable of activating TLR-2 [39]. Oral administration of Lctbs reuteri attenuated major characteristics of an asthmatic response, including airway eosinophilia, local cytokine responses and hyperresponsiveness to methacholine. This effect of Lctbs reuteri on the allergic airway response was found to be dependent upon TLR-9 [40]. Furthermore, TLR stimulation was also thought to occur after probiotic administration in infants with eczema who showed increased levels of serum C-reactive protein (CRP), IL-10 and IgE [41].

Treg production.  In a food allergy mouse model, oral administration of Bfdbm bifidum and Lctbs acidophilus suppressed OVA-specific IgE production, which was caused by inducing Treg-associated TGF-β production [42]. Another study demonstrated that neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of Tregs and TGF-β production [43]. As mentioned previously, Lctbs reuteri/casei have also been shown to prime monocyte-derived DCs through the DC-SIGN to drive the development of Tregs[38]. Interestingly, the probiotic combinations are alleged to cause a paradoxic Th2 stimulation, almost the same as in chronic and balanced helminth infection, which is associated with activation of Tregs suppressing allergic inflammation. Because colonization is transient, the Treg induction is not permanent. Thus, when these immunological effects no longer operate, the clinical effect is simultaneously lost. For instance, when helminth infections are treated, the prevalence of allergic sensitization increases rapidly. This is also a plausible explanation for the fading probiotic effect [44].

In summary, local influences of probiotics potentially include reduction of permeability and systemic penetration of antigens, increased local IgA production and alteration of local inflammation or tolerance induction. Some possible systemic effects consist of anti-inflammatory effects mediated by TLRs, Th1 skewing of responses to allergens and activation of tolerogenic DCs, in addition to Treg production.

Descriptive studies showing the role of probiotics in atopic/allergic diseases

The increased prevalence of atopic diseases is defined currently as an epidemic. AD, known as the earliest of these conditions, might act as an indicator for the development of IgE-mediated atopic manifestations. Thus, being aware of possible measures, such as probiotic use, to prevent and/or heal atopic disease is essential for the practising allergist. The various effects of different probiotic strains in allergic diseases are summarized in Table 2.

Table 2.  The various effects of different probiotic strains in allergic diseases are shown from laboratory and clinical studies referred to in the text.
ReferencesProbiotic strainType of allergic diseaseOutcome
  1. ↑: Increase in symptoms or negative effect; ↓: decrease in symptoms or positive effect; ↔: no change in symptoms or no effect; Bfdbm: Bifidobacterium; JCP: Japanese cedar pollinosis; Lctbs: Lactobacillus; LGG: Lctbs rhamnosus GG; VSL#3: probiotic mixture; OVA: ovalbumin.

  Atopic dermatitis (eczema) 
Sistek et al.[31]Lctbs rhamnosus + Bfdbm lactisFood-sensitized atopic children
Kalliomäki et al.[45]Lactobacillus GGAtopic dermatitis
Kopp et al.[46]Lactobacillus GGAtopic dermatitis↔, ↑
Wickens et al.[47]Lctbs rhamnosusIgE-associated eczema
Viljanen et al.[41,48]LGGAtopic eczema/dermatitis syndrome
Rosenfeldt et al.[49]Lctbs rhamnosus + Lctbs reuteriAtopic dermatitis
Kuitunen et al.[50]Lctbs + Bfdbm + propionibacteriaIgE-associated allergy
Boyle et al.[54]VariousEczema
Lee et al.[55]VariousAtopic dermatitis
Soh et al.[63]Bfdbm longum + Lctbcs rhamnosusEczema and atopic sensitization
  Food allergy and anaphylaxis 
Kim et al.[27]Lctbs acidophilus + Bfdbm lactisOVA-induced allergic symptoms
Isolauri et al.[56]Bfdbm or LctbsFood allergy
Majamaa et al.[57]LGGFood-sensitized eczema
Shida et al.[60]VSL#3 + Lctbs casei strain ShirotaAnaphylaxis with food allergy
Hol et al.[61]Lctbs casei + Bfdbm Bb-12Cow's milk allergy
Taylor et al.[62]LGG or Lctbs acidophilusCow's milk allergy↔, ↑
  Allergic rhinitis 
Di Felice et al.[59]VSL#3Allergic rhinitis
Giovannini et al.[67]Lctbs caseiAllergic rhinitis
Morita et al.[69]LGG + Lctbs gasseriAllergic rhinitis
Xiao et al.[71]Bfdbm longumAllergic rhinitis; JCP
Tamura et al.[72]Lctbs casei strain ShirotaAllergic rhinitis; JCP
Kruisselbrink et al.[33]Lctbs plantarumDermatophagoides (Der p1) sensitization
Feleszko et al.[43]Bfdbm-12Airway reactivity
Blümer et al.[73]LGGAllergic asthma
Repa et al.[74]Lactococcus lactis + Lctbs plantarumBirch pollen allergen (Bet v1) sensitization
Karimi et al.[75]Lctbs reuteriAllergic airway inflammation
Helin et al.[78]LGGPollen allergy

AD (eczema).  Hitherto, there have been several published double-blind, randomized, placebo-controlled trials that showed a preventive effect of LGG on atopic disease in a high-risk population. The Finnish study was the first report to describe that the frequency of AD in the probiotic group was half that of the placebo [45]. Nevertheless, these results have been questioned recently by a trial conducted by an Australian group, who reported no difference in the development of AD, but observed increased sensitization to allergens in neonates supplemented with a different Lctbs strain [46]. Taken together, these studies suggested that probiotics may not be effective for all atopic children, but might offer benefit in a subset of IgE-sensitized children.

IgE-sensitized (atopic) versus non-IgE-sensitized (non-atopic) eczema.  In support of the efficacy of probiotics in IgE-sensitized children, some other studies have also demonstrated comparable results. Treatment with Lctbs rhamnosus for the first 2 years of life was associated with a significant reduction by approximately half in the prevalence of any IgE-associated eczema [47]. Another study demonstrated that LGG alleviated atopic eczema/dermatitis syndrome symptoms in IgE-sensitized infants [48]. The beneficial effect of two Lctbs strains (rhamnosus and reuteri) in children with AD was also shown. This effect was more pronounced in patients with a positive skin prick test and increased IgE levels [49]. In caesarean-delivered children, probiotic use has been shown to prevent IgE-associated allergy until the age of 5 [50]. In food-sensitized atopic children, the efficacy of the probiotics such as Lctbs rhamnosus and Bfdbm lactis was also demonstrated [31].

Additionally, a review evaluating 13 randomized controlled trials (RCTs) concerning routine probiotic use in the treatment or prevention of AD proved effective. This study, in which 10 of the 13 RCTs evaluated probiotics as treatment and three for prevention, concluded that regardless of IgE-sensitization, probiotics, especially LGG, were effective in the prevention of AD [51]. A meta-analysis assessing six studies reported significant benefits in enrolled infants at high risk of allergy who were put on probiotic supplements containing Lctbs rhamnosus[52]. Another meta-analysis of 11 studies that focused upon paediatric AD demonstrated that probiotics are effective in the prevention of AD [53].

However, some other studies failed to demonstrate that the severity and frequency of allergic diseases were decreased with the supplementation of probiotics, regardless of their IgE sensitization status. For instance, Boyle et al. and others could not show any effect even for LGG in infants with AD [54]. A few meta-analyses also could not confirm that IgE sensitization was indeed a factor in determining the efficacy of probiotics in atopic children [54,55]. However, the heterogeneity between studies may be attributable to probiotic strain-specific effects, meaning that some probiotic strains may still have a therapeutic role in eczema [54].

Food allergy and anaphylaxis.  Because food allergies are thought to be central in the pathogenesis of AD, targeting the enteric mucosa, the primary route of food antigen contact and sensitization, with probiotics might influence crucial mechanisms. There have also been several published studies showing that oral administration of Bfdbm or Lctbs strains could alleviate the food allergy [56]. In another study, Lctbs acidophilus and Bfdbm lactis treatments prevented OVA-induced allergic symptoms on the skin and gastrointestinal tract, e.g. eosinophilic infiltration [27]. Previous studies showed that administration of the probiotic LGG to highly selected food-allergic patients (age < 2 years, challenge-proven and mild-to-moderate eczema) improved the eczema score significantly [57]. Studies in infants with eczema who received formulas supplemented with LGG have shown benefit in decreasing gastrointestinal symptoms [58]. In addition, oral therapy with the probiotic mixture VSL#3 and Lctbs casei strain Shirota were able to reduce anaphylactic symptoms in a food allergy model [59,60].

In contrast, supplementation of Lctbs casei and Bfdbm Bb-12 to extensively hydrolyzed formula did not accelerate cow's milk tolerance in infants with cow's milk allergy [61]. Moreover, a few RCTs also showed no effects of probiotics, specifically LGG or Lctbs acidophilus, in protection against cow's milk allergy in infancy [54,56,62,63]. Osborn et al. reviewed six studies enrolling 1549 infants and reported no other benefits of probiotics for food hypersensitivity [52].

Allergic rhinitis.  Probiotic treatment in patients with seasonal and perennial allergic rhinitis (AR) showed clinical improvement in most of the published studies [53,64]. The majority of the RCTs showed a reduction in symptom severity and decreased use of relief medications [65,66]. Moreover, the immunomodulatory activity of the probiotic mixture VSL#3, studied in mouse models of allergic sensitization with inhalants, prevented the development of Parietaria major allergen-specific local and systemic response when delivered intranasally [59]. Twelve-month consumption of fermented milk containing Lctbs casei improved the health status of children with AR [67]. Furthermore, the fermented milk prepared with LGG and Lctbs gasseri was found to be beneficial in a seasonal AR such as in Japanese cedar pollinosis (JCP), due to its effect on nasal blockage [68,69]. Intake of Bfdbm longum-supplemented yogurt also relieved JCP symptoms [70,71]. A meta-analysis by Vliagoftis concluded that all the trials studied in children showed improvement in clinical outcomes [53].

Nonetheless, one study suggested that fermented milk containing Lctbs casei strain Shirota does not prevent allergic symptoms in patients sensitive to JCP, although the addition of the strain may delay the occurrence of allergic symptoms in patients with moderate-to-severe nasal symptoms [72]. A meta-analysis evaluating six relevant studies also reported no other benefits of probiotic use for any allergic disease [52].

Asthma.  Some researchers demonstrated that LGG may exert beneficial effects on the development of experimental allergic asthma, when applied at a very early phase of life. For example, in one study, perinatal maternal application of LGG suppressed allergic airway inflammation in mouse offspring [73]. Additionally, in these offspring that were supplemented with maternal LGG, the allergic airway and peribronchial inflammation, as well as goblet cell hyperplasia, were reduced significantly [73]. In another mouse model, the administration of either Bfdbm-12 or LGG suppressed all aspects of the asthmatic phenotype, including airway reactivity, antigen-specific IgE production and pulmonary eosinophilia [43]. A few other studies showed the following: intranasal administration of Lctbs plantarum suppressed antigen-induced Th1 and Th2 immune responses in Der p1-sensitized animals [33]. Co-application of Lactococcus lactis and Lctbs plantarum with the major birch pollen allergen (Bet v1) caused suppression of allergen-induced basophil degranulation [74]. Finally, oral administration of live Lctbs reuteri attenuated major characteristics of an asthmatic response, including airway eosinophilia, local cytokine responses and hyperresponsiveness to methacholine in a mouse model concerning allergic airway inflammation [40,75].

A recent study showed that interactive treatment using acupuncture and probiotics has a beneficial clinical effect on bronchial hyperreactivity in children with asthma and might be helpful in the prevention of acute respiratory exacerbations [76]. However, adolescents suffering from pollen allergy did not benefit from LGG administration [77,78]. Furthermore, Osborn et al. reviewed six studies and reported no other benefits for any other allergic disease [52]. A review concluded that trials of the effects of probiotics on asthma are few and show inconsistent results, thus a decision on the benefits of probiotics cannot be reached, although some positive experimental evidence from animal studies suggests the need for further investigation [53].

Pitfalls (side effects) of probiotics use

A joint FAO/WHO report on the evaluation of probiotics in food stated that ‘documented correlations between systemic infections and probiotic consumption are few, and all occurred in patients with underlying medical conditions’. The safety of Bfdbm lactis is documented in infants from birth and in vulnerable populations, such as preterm infants, malnourished infants and infants born to mothers with human immunodeficiency virus (HIV) disease. Additionally, Bfdbm lactis is the only probiotic bacterium that has undergone FDA evaluation for use in infant formulas from birth that can be commercialized for this application [79]. LGG also seems generally safe and to be a probiotic appropriate for older infants/children.

  • • Clinical benefit of probiotic therapy depends on numerous factors, such as type of bacterium (as shown in Tables 1 and 2), dosing regimen, delivery method and other underlying host factors, e.g. the age and diet of the host.
  • • Probiotics might cause sepsis in immunocompromised populations. Lctbs septicaemia has been reported in two children with short bowel syndrome receiving LGG supplementation [80]. Children with abnormal immune function, premature infants, immunocompromised hosts and those with indwelling central lines and autoimmune disorders should use these products with caution [81].
  • • An increased rate of recurrent wheezing episodes [46].
  • • An augmented rate of atopic disorders [9].
  • • Increased sensitization to allergens [45,46,62].
  • • Adverse gastrointestinal symptoms, e.g. diarrhoea, due to heat-inactivated LGG supplementation.

Highlights of probiotics use

  • • There are very promising literature data recommending the addition of probiotics to infant feeds for prevention of allergic disease or food hypersensitivity.
  • • Clinical improvement, especially in AR and IgE-sensitized (atopic) eczema, has been reported in most of the published studies.
  • • Enhanced response to some vaccines is demonstrated in children taking LGG [82,83].
  • • Decrease in the number of respiratory infections is also demonstrated in children receiving LGG [76,84].

Why inconsistent results in some studies?

As discussed in detail above, the value of probiotics for primary prevention is controversial. Published trials vary considerably in study design, including applied probiotics type (e.g. killed/live or species such as Lctbs or Bfdbm) or time (postnatal/prenatal) and period of probiotics supplementation, thereby limiting comparability of the results. Mixing probiotics with prebiotics or a hydrolyzed whey formula or using probiotic combinations also might play a role in confusing the results of different studies. No two probiotics are exactly alike, and therefore researchers should not expect reproducible results from studies that employ different species or strains, variable formulations and diverse dosing schedules (Tables 1 and 2). Additionally, host factors (including genetic differences in microbial responses and allergic predisposition) and other environmental factors such as general microbial burden, individual microbiota, diet (including consumption of prebiotic substances) and treatment with antibiotics are other major factors that can affect results.


There is a large amount of conflicting data on the preventive and therapeutic effects of probiotics in atopic diseases. Results from meta-analyses and systematic reviews that combine results of studies from different types of probiotics to examine the effects in any disease should be interpreted with caution. We should also accept the difficulties of recognizing allergy and allergic diseases, which have many phenotypes, such as in atopic and non-atopic asthma and eczema. Thus, probiotics cannot be recommended generally for primary prevention of atopic disease. Additionally, if probiotics are used in atopic infants/children for any reason – therapy or prevention – a cautionary approach should be taken. Following these guidelines, Bfdba, particularly Bfdbm lactis, has a uniquely strong safety profile, making it a good probiotic candidate for newborns and young infants. No probiotics should be used in immunocompromised children, even if they have atopic diseases or are at risk. Finally, there is insufficient but very promising evidence to recommend the addition of probiotics to foods for prevention and treatment of allergic diseases.

Future expectations

Better understanding of the effects of different probiotic strains and a deeper insight into the mechanisms of the heterogeneous manifestations of atopic disease are needed for the validation of specific strains carrying anti-allergic potential [54]. Therefore, research activities are focusing currently upon identification of specific probiotic strains with immunomodulatory potential and upon how dietary content interacts with the most efficacious probiotic strains [85]. Moreover, selection of the most beneficial probiotic strain, the dose and the timing of supplementation still need to be determined [54]. Further studies should also clarify if any susceptible subgroups of atopic diseases exist, and how these subgroups benefit from supplementation with certain probiotic strains.