Since conventional allergy medication for asthma or allergic rhinitis (AR) can cause side effects which limit the patients’ quality of life, it is of interest to find other forms of therapy. In particular, probiotic bacteria, such as Lactobacillus species, have shown anti-allergic effects in various mouse and human studies. For instance, administration of some Lactobacillus species resulted in nasal and ocular symptom relief and improvement of quality of life in children and adults suffering from rhinitis. Different changes in cytokine profiles, such as elevated Th1 and decreased Th2 cytokines, reduced allergy-related immunoglobulins and cell immigration have been found in both human and murine studies. Positive effects on patients like less activity limitations or fewer rhinitis episodes and longer periods free from asthma or rhinitis were also described following oral administration of Lactobacillus bacteria. However, it is still unclear how this type of lactic acid bacteria leads to changes in the immune system and thus inhibits the development of allergies or relieves their symptoms. This review gives an overview of current studies and draws conclusions concerning the usage of probiotic Lactobacillus strains in AR.

The “Allergic Rhinitis and its Impact on Asthma” (ARIA) guidelines classify allergic rhinitis (AR) as “intermittent” or “persistent” disorder, depending on the presence of symptoms within 4 weeks. Sometimes, the terms “seasonal” or “perennial” are connected with AR, instead of “intermittent” or “persistent” [1]. The severity of symptoms is defined as “mild” or “moderate/severe” depending on the impact on the quality of living [2]. The term hay fever is also often used as a synonym for AR [3]. Yet, not only outdoor allergens like grass or tree pollen cause AR but also indoor allergens such as animal hair or house dust mites (HDM) [2, 3]. Common symptoms of patients with this allergic disorder are rhinorrhea, nasal congestion or blockage, sneezing, watery or itchy or red eyes, and nasal itching [2, 4]. Additionally, the quality of life of patients with AR may be reduced as there are several comorbidities, for example, asthma or sinusitis [4]. One main goal of the AR management is to reduce the dosage and the frequency of medication. For instance, second-generation antihistamines or steroids are often prescribed as a long-term treatment for AR patients. Possible side effects of long-term treatment with allergy medication can be drowsiness, gastrointestinal disorders, dry mouth, dizziness, headache, or infections [5]. Additionally, the window of effectiveness of these drugs is often limited by the time after the onset of an allergy. Besides, it is important to develop a safe, lifelong therapy for the prevention of allergic reactions. In this regard, food with live and heat-killed probiotic strains would be a suitable option as both likewise alleviate symptoms of AR [5, 6]. Probiotics are described as “live microorganisms” with a “health benefit on the host,” when “administered in adequate amounts” [7]. With their long track records for safety, strains of Lactobacilli and Bifidobacteria are widely used [8] and administered as drugs, medical or probiotic food [9]. Lactobacillus species belong to the so-called lactic acid bacteria (LAB), which produce bacteriocins and competitively exclude potential pathogens [9, 10]. In response to LAB administration, beneficial effects on the host were found such as modulation of immune responses with increased Th1 cytokines in mice fed with L. casei Shirota [10], lowered Th2/Th1 ratios following giving L. delbrueckii in yoghurt [11], or diminished Th2 cytokines after oral administration of B. lactis [12]. Further, L. acidophilus [13] and B. lactis [12] are described to reduce allergic nasal symptoms.

This review comprises 31 studies, 18 human trials and 13 mouse studies, which were selected from PubMed by a literature search using the key terms Lactobacillus AND Allergic Rhinitis, Lactobacillus AND Pollen Allergy, and Lactobacillus AND House dust mite. Research studies without clearly defined inclusion criteria, such as clinically diagnosed AR, were excluded. A general overview of the obserevd effects of probiotic Lactobacillus strains in the analyzed animal and human trials is presented in Table 1.

Table 1.

Effects of Lactobacillus strains in animal and human studies [5, 6, 11, 14, 17, 18, 20-24, 26, 27, 32, 35-39, 41, 44-46, 50, 51, 53, 60, 66]

Effects of Lactobacillus strains in animal and human studies [5, 6, 11, 14, 17, 18, 20-24, 26, 27, 32, 35-39, 41, 44-46, 50, 51, 53, 60, 66]
Effects of Lactobacillus strains in animal and human studies [5, 6, 11, 14, 17, 18, 20-24, 26, 27, 32, 35-39, 41, 44-46, 50, 51, 53, 60, 66]

Treatment with probiotic strains, such as L. paracasei, L. acidophilus, L. casei Shirota, L. helveticus, L. rhamnosus GG (LGG) showed alleviation of symptoms in AR or HDM patients. Generally, Lactobacillus bacteria studies were performed with adult or adolescent [6, 13-19] and numerous with young [20-26] AR patients. Table 2 presents human trials, which analyzed the effects of Lactobacillus strains on AR symptoms. 11 studies showed significant effects [6, 13, 14, 17, 18, 20, 21, 24-27], 3 did not [16, 19, 23]. In some studies, the effects of probiotics, taken alone or in combination with clinical medication, were evaluated [18, 20, 24]. In the study by Costa et al. [18], L. paracasei LP-33 was given as an add-on therapy to patients with AR symptoms during grass pollen season, who were currently treated with the antihistamine loratadine (10 mg/daily) [18]. The verum group had an additional improvement of 17.7% in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) global score compared to the placebo group (p = 0.0255). Although no significant differences were measured for nasal symptoms in RQLQ, but ocular symptoms changed positively for the L. paracasei group (p = 0.0029; −1.75 ± 1.63 vs. placebo −1.36 ± 1.77). In another study, levocetirizine (5 mg) with or without L. paracasei (LP HF.A00232; 5 × 109 colony-forming units [CFU]/capsule) was used in children diagnosed with perennial AR [20]. Here, L. paracasei plus levocetirizine as a rescue medication showed a “synergistic effect” and led to lower individual symptoms for sneezing (p = 0.005), itchy nose (p = 0.040), or swollen puffy eyes (p = 0.038). Although there were no additional effects of L. paracasei when taken with levocetirizine, symptoms were relieved even after termination of medication intake. Additionally, the amount of taken antihistamines in the probiotic group decreased about 56% within the study period (100% week 1–8 vs. 43.35 ± 38.53% weeks 10.5–12) [20]. Ahmed et al. [24] demonstrated equal effects for cetirizine and LP-33 in children younger than 5 years suffering from perennial AR. Over 90% of these children showed symptoms, for example, rhinitis, sneezing, or nasal blocking. After 6 weeks of intervention, with either daily intake of probiotics (LP-33, 2 × 109 CFU) or cetirizine (2.5–5 mg), baseline symptoms of AR significantly improved in over 95% of all participants. Nasal blocking was reported to be fully improved in the probiotic group in 84.6% (88 of 104 patients) versus 85.5% (89 of 104 patients) in the cetirizine group. Other bothersome symptoms of perennial AR, such as rhinorrhea or sneezing, were equally alleviated, with no difference in treatment outcome [24]. Thus, L. paracasei seems to support the effect of clinical AR medication as an add-on therapy [18, 20] or could be even effective as AR medication [24].

Table 2.

Effects of Lactobacillus strains on AR symptoms in humans

Effects of Lactobacillus strains on AR symptoms in humans
Effects of Lactobacillus strains on AR symptoms in humans

Several studies with permitted use of asthma and allergy medication reported controversial results [13, 19, 21]. Giovannini et al. [21] found 33% less rhinitis episodes in the Lactobacillus group without any change in usage of medication during the study irrespective of the treatment protocol. A study on L. acidophilus L-92 [13] demonstrated significant alleviation of nasal symptoms medication score. It also demonstrated a beneficial trend for ocular symptom medication scores in the probiotic group compared with the control group. In contrast, Helin et al. [19] did not find alleviative effects of oral-administered bacteria. However, this study had a population of only 18 patients; therefore, the results should be viewed with caution.

Apart from nausea in some participants, no severe side effects were mentioned related to the intake of L. paracasei strains [24]. Therefore, this kind of probiotic treatment seems to be beneficial for patients suffering from perennial AR as it improves their quality of life by reduction of bothersome symptoms [24]. The study duration of 5–12 weeks was relatively short compared to another study with a duration of 1 year or longer. Thus, to support evidence, longer studies with a larger population are necessary. Only 1 study used AR medication without the combination with probiotics [24]. Another study suggested the probiotic effect in their study could have been influenced by the use of medication, and even a follow-up period of 4 weeks without medication intake was maintained to exclude this effect in an optimal way [20].

The administration period seems to be another important factor in the oral immunization against allergens and so for prevention of AR. For instance, L. casei showed most increased IgA + cell amounts versus control animals after 5 days of probiotic intake (p < 0.001), which could be due to the B-cell homing mechanism [28]. Allergen-specific immune response was also reduced when probiotics were taken after sensitization with birch and grass pollen, and less inflammation occurred [29]. Prevention of lung inflammation was also visible with L. paracasei NCC2461 and B. longum NCC3001 as they showed regulated systemic allergic responses after an application at the time of sensitization [29]. To evaluate preventive effects of Lactobacillus intake related to AR, some studies have gone further and focused on perinatal application [26, 27, 30]. LGG treatment was a good preventor of atopic diseases in infants of atopic parents with AR, asthma, or eczema [27]. Here, the form of administration, maternal intake of the probiotic capsule and breastfed children, or probiotic intake by infants themselves did not significantly influence the preventive effect of LGG (p = 0.74). Not only studies with children or pregnant women were conducted estimating protective effects but also with adults. L. paracasei ST11 had positive effects on patients suffering from grass pollen AR. For example, subjective nasal congestion (p = 0.04), IL-5 (p = 0.03), or IgG4 (p = 0.049) was reduced after the consumption of probiotic fermented milk compared with the placebo group [14]. Probiotics are even recommended by the WHO for pregnant women and their infants at high risk of having an allergic child or developing allergies, to prevent children from having eczema [31].

In few human studies, immunological and clinical parameters were assessed [13, 14, 16, 17, 20, 21, 23, 27]. Findings of significant changes of immunological outcome factors of these human trials are presented in Table 3. One factor for the occurrence of allergic airway diseases, such as AR, is a disturbed balance between Th1 and Th2 cells, with a majority of Th2 cells [32, 33]. Th1 cytokines, IFNγ and IL-12, have been found to be downregulated in AR patients [34]. A significant decreased Th2 cytokine profile in response to probiotic treatment was found in 5 animal trials [35-39]. Moreover, significantly higher levels of IFNγ were found after the intake of L. plantarum [36], L. helveticus, and L. gasseri [35], and in vitro experiments with L. plantarum birch pollen allergy in a murine model showed similar augmenting effects on IL-12 and IFNγ [37]. In a human study with children, increased IFNγ levels were found after the intake of probiotics, in particular 2 Bifidobacteria strains and L. acidophilus AS031, and significantly improved TGFβ levels correlated with less atopic dermatitis occurrence [40]. But the role of probiotics in connection with IFNγ in allergic inflammation is still not clearly identified as the IFNγ production in the probiotic group in a human trial showed a significant decline [41].

Table 3.

Changes of immunological parameters in humans following treatment with Lactobacillus strains

Changes of immunological parameters in humans following treatment with Lactobacillus strains
Changes of immunological parameters in humans following treatment with Lactobacillus strains

In a dose-depended manner, Gram-positive bacteria like L. plantarum NCIMB8826, L. lactis MG1363, L. casei ATCC393, and LGG hindered the production of Th2 cytokines IL-4 and IL-5 [42]. In vitro experiments showed strain-dependent effects of about 100 tested LAB strains [43]. IL-12 was used as a parameter for Th1 activity, while IL-4 was used for Th2 activity. As a whole, some strains were proved to be better IL-12 inducers or IL-4 repressors than others. For example, L. paracasei KW3110 was a good IL-12 inducer and IL-4 inhibitor. Therefore, LAB seems to have the ability to intervene in the Th2 cytokine production pathway and to balance out the Th1/Th2 cytokine levels, which consequently could help prevent allergies [43]. Not only the latter animal model [43] showed effects of LABs on the cytokine profile but several others demonstrated a Th2 cytokine-diminishing effect due to Lactobacillus treatment (see Table 1).

The considerable reduction of IgE levels in animal studies [32, 36, 38, 39, 44, 45] and in human trials [22, 23, 41, 46] indicates a reduction of IgE-producing B cells by Lactobacillus bacteria. In vivo experiments with L. paracasei KW3110 revealed significant lower total IgE and reduced antigen-specific IgE levels (p < 0.05) than control animals without oral administration of this type of LAB [43]. The findings of Makino et al. [35] did not support this consideration because OVA-specific IgE levels were not significantly suppressed by the intake of probiotic L. helveticus H2171, although face-scratching and sneezing could be alleviated by almost one third compared to the control group. The same effect on allergic response was demonstrated in an OVA sensitization murine model with fermented yoghurt, containing bacterial starter cultures such as L. bulgaricus, S. thermophilus, and L. paracasei CNCMI-1518 (each 108 CFU/mL) [47]. In human trials, results are inconsistent. On the one hand, a small placebo-controlled study with L. casei Shirota demonstrated decreased IgE (p = 0.05) and enhanced early grass pollen-specific IgG (p < 0.01) in seasonal grass pollen-allergic rhinitis. On the other hand, only diminishing modification of birch pollen-specific IgE and none of birch pollen-specific IgG or IgG4 levels was found in response to probiotic treatment in other studies [22, 46]. In addition, Wassenberg et al. [14] found significant increased subjective nasal congestion by means of visual analog scale after treatment with L. paracasei ST11 (p = 0.04) without any measured change in grass pollen-specific IgE or IgG levels compared to placebo. Another mechanism, rather than just the IgE suppression, seems to be important for alleviation of allergic symptoms. A correlation between both immunoglobulins IgE and IgG could be seen. Symptoms were relieved due to blocked IgE binding and higher levels of IgG [48]. This could be one explanation for reduced allergy symptoms without lessened IgE levels as IgG was found to possibly block IgE binding activities [48].

Foxp3-positive regulatory T cells (Treg) and their mediators IL-10 and TGFβ play a major role in a balanced immune response with an inhibitory effect on eosinophils, mast cells, and basophils [49]. Significant effects of Lactobacillus strains on Treg were demonstrated in both animal and human studies [22, 50, 51]. For instance, Lactobacillus treatment was associated with expanded IL-10 levels [5, 46, 51], such as the increase in the IL-10 level about 24 ± 13% in response to intervention with L. plantarum [46]. In contrast, no associations of increased IL-10 levels and other species such as L. reuteri, L. gasseri, and L. johnsonii could be found [52]. Likewise, LGG showed contradictory results as the intake of this specific strain was related to an increase in IL-10 levels in 1 study [51] and decreased levels in another animal model [53]. A significant expansion of the Treg/Th2 ratio was demonstrated in response to treatment with L. plantarum NIZ02877 (38%) and L. plantarum CBS125632 (68%) [46]. The expression of the transcription factor Foxp3 was upregulated in a preventive birch pollen allergy model in young mice with L. paracasei-treated mothers (p < 0.001) [53]. Also, Yamashita et al. [5] showed the same enhancing effect on Foxp3 (p < 0.001) and IL-10 levels (p < 0.01) in response to treatment with L. helveticus LH2171. The same strain was related to amplified IL-10 levels, reduced Th2 cytokines (IL-4, IL-13; p < 0.05), and positive effects on sneezing and face-scratching [35].

Additionally, allergic reactions could be influenced by regulating co-stimulatory molecules, such as CD40 or CD80. These are important for T-cell responses [43] and IgE production [33]. Inhibition of antigen-presenting cells by means of reduced CD80+ cells was found in an AR mouse model with L. crispatus KT-11 treatment [39]. In murine peribronchial lymph nodes, treated with OVA + LGG, less CD40 and significantly lowered CD86 molecules were detected [51]. Not only fewer active DC cells were found after Lactobacillus intervention in animal and human trials but also the infiltration of eosinophils and neutrophils and the amount of macrophages in the upper respiratory tract were influenced by probiotics [50].

It is widely known that a rebalanced gut microbiota can have positive effects on airway diseases and also alleviate gut inflammation [50]. The correlation of airway inflammation and gut microbiota disorder was investigated in 1 study [51]. LGG introduced a beneficial, significant increase in phylum Bacteroidetes (p < 0.01) and lowered Firmicutes [51]. In the same study, a decline in inflammatory eosinophils and neutrophils, less mucus hyperplasia, and decreased Th2 cytokines, IL-4 (p < 0.05) and IL-13 (p < 0.01), were found. Similarly, results were shown with the probiotics B. longum and L. plantarum in HDM-induced AR [50]. An important part of the mucosal barrier is IgA [22, 54]. Increased IgA levels were found in several studies [22, 23, 53]. Moreover, mice pretreated with recombinant LAB showed lowered IgE and increased specific IgA levels [44]. As this effect is usually known for allergen-specific immunotherapy [49], probiotics with these kinds of immunoglobulin modulation characteristics can be helpful to prevent allergies. Probiotics such as Lactobacillus bacteria are known not to be stable gut microbiota inhabitants [55]. Hence, the modulative effect of LAB is possibly not only due to a balanced microbiota itself but combined with immunological changes.

This overview supports the assumption that administration of Lactobacillus strains could positively affect AR patients by alleviating allergic symptoms. Negative effects were not reported; thus, the treatment with probiotic Lactobacillus strains appears to be suitable for AR patients. However, the comprised studies differ widely in used Lactobacillus strains, amount of administered Lactobacillus bacteria, form and duration of administration, accompanied therapy, and measured parameters.

In some study protocols, 1 Lactobacillus strain was used, while in others, different probiotics were combined or added to dairy products with several starter cultures. There is less information about a most suitable Lactobacillus candidate in connection with AR in human trials [46]. Consequently, studies evaluated the effect of different probiotic bacteria in vitro, followed by in vivo experiments with the most effective strains in animal [43] or human trials [46]. Snel et al. [46] used 5 different Lactobacillus strains in an out-of-season human trial with birch pollen to evaluate their effects. While the intervention groups had a small number of participants (n = 9–11), the results of this trial gave a hint on the possible beneficial effects of the used strains like the reduction of IgE or Th2 cytokines (IL-5 and IL-13) and an increase in anti-inflammatory cytokine IL-10. These results could be useful for enlarged study protocols. Another important factor for the evaluation of Lactobacillus effects in AR is the strain-specific limited survival in the human gastrointestinal system [56]. For example, orally administrated L. casei in fermented milk could be found in feces of humans [56, 57], while viable L. delbrueckii subsp. bulgaricus could not be detected in all subjects after yoghurt ingestion at all times [58].

It is widely known that possible beneficial effects of any consumed probiotics such as Lactobacillus bacteria depend on their capability to survive different conditions during gastroduodenal transit like bile acids, pH, or enzymes. The probiotic effect is commonly accepted with a daily consumption of minimum 106 CFU/mL or gram of probiotics [59]. However, different effects on immunological and symptomatic parameters might be due to the used amount of Lactobacillus bacteria, which varied in the considered human trials from 108 CFU/mL [21] up to 3 × 1010 CFU/100 mL daily [13]. Moreover, the form of administration was not homogenous. Lactobacillus strains were given orally, but even here in different forms: capsules [6, 18-20, 23, 26, 27], yoghurt [21, 22], dairy drinks or milk [13-15, 46, 60], or tablet or sachet [17, 24] (see Table 2). Half of the considered human trials used capsules, revealed significant positive effects on nasal or ocular symptoms, and reduced the risk in hay fever or atopic eczema. But also, dairy products and yoghurt reduced allergy-related immune parameters such as IL-13, IgE, or improved AR symptoms. But yoghurt as a form for administration seems to be not ideal for investigating probiotic effects as it was ascertained to have beneficial effects on patients with allergic rhizopathy after daily intake for 4 months [61]. Numerous studies, such as Del Piano et al. [62], investigated the effect of different probiotic application forms. An improved resistance to gastroduodenal conditions with encapsulated bacteria in contrast to less effective nonencapsulated bacteria was found. Here, a good protective coating is proposed to support the beneficial effects even with a reduced amount of used cells [62]. Otherwise, 2 studies with L. plantarum 33, the same duration of 30 days, but different application forms (fermented milk [60] or capsules [6]) found similar positive effects on the quality of life or level of bother in their subjects. Normally, Lactobacillus bacteria are regarded as safe, and minor side effects were suffering from flatulence [63] or nausea [24]. But the form of administered bacteria should be chosen with mindful consideration because modulative effects in the immune system can be delicate for patients on immunosuppressive therapy [63]. Therefore, it is difficult to suggest which kind of application form is the most efficient one for all AR patients.

Moreover, the effect of probiotic Lactobacillus strains is difficult to access if in studies, the intake of antibiotics, of allergy or asthma medication was allowed [16, 19, 64]. Others did not even mention handling of medication before, during, and after treatment periods with Lactobacillus strains. Self-medication was permitted during symptoms, but this makes the significance of probiotic effects more complicated. It is a matter of common knowledge that especially antibiotics can unbalance the gut microbiota and therefore be one factor of developing allergic or inflammatory diseases [65]. The intake of dairy products containing probiotics within the study period was also handled in a completely different manner. However, the permitted use of medication or probiotic products can possibly mask effects of simultaneously taken Lactobacillus bacteria.

Another restraining factor for answering the question of possible effects of Lactobacillus bacteria on the organism is different outcome measures in studies related to AR. Some studies [18, 19, 24, 26, 60] used only questionnaires and no immunological parameters for evaluation of changed allergic symptoms. The results of studies without immunological tests are less conclusive. Questionnaires as a measuring tool provide rather subjective results or actually have been modified by the authors [6]. Also, the assistance of parents in studies with children for filling out the surveys might have an impact on the results of clinical outcomes.

Factors related to the type of application, such as duration and timing of intake, seem to vary between the probiotics. The beginning of the probiotic intake varied from months before pollen season to the onset of pollen season. Moreover, the duration of LAB consumption in human trials differed from 2 weeks [27] to 12 months [21]. Figure 1 provides an overview of most of the intervention strategies and concepts used in the studies. For example, with L. paracasei NCC2461 and grass pollen-allergic rhinitis, different studies were conducted. Nembrini et al. [16] could not find significant changes of nasal symptoms with these Lactobacillus bacteria during the pollen season, whereas alleviative effects in nasal symptoms as well as enhanced cytokine secretion of IL-5, IL-8, IL-10, or IL-13 in pollen-stimulated peripheral blood mononuclear cells could be found in 2 out-of-pollen season studies [14, 17]. There was 1 placebo-controlled trial with an intake of LGG over 5.5 months [19]. Here, the intake started 2.5 months prior pollen season and participants were then asked to take the probiotics for 1 month during pollen season. The study ended 2 months afterward. Although it was a longer period over several months within and outside the season, which would suggest immunomodulatory effects, there was no significant alleviation of symptoms in response to treatment with LGG. The symptom scores increased in both groups, and thus, a positive effect of LGG could not be attributed. Still, in this study immunological parameters for the relation of symptomatic and immunological effects were not measured and the cohort was small (n = 36) [19]. Another trial, starting prior to pollen season and ending afterward, with L. acidophilus and B. lactis had no significant impact on total AR symptoms, but a reducing effect on inflammatory-related immune parameters, such as IL-6 or TNFα [23]. Therefore, an intake prior to the start of pollen season could be a good strategy for AR patients, but it is still unclear which probiotics are most effective and how long the probiotics should be taken. It is often desirable to have long-term investigations to investigate the effects of Lactobacillus bacteria on AR patients, and the LAB consumption period in the analyzed human studies was from just 2 weeks [27] up to 1 year [21]. The intake of medication due to prevailing symptoms is understandable, but it is questionable if allergic patients would consume probiotic products without having any symptoms for a long time.

Fig. 1.

Overview of study concepts for administration of Lactobacillus strains in AR. CFU, form and duration of administration, timing (in – or out of – allergen season), and additional medication are shown. CFU, colony-forming units.

Fig. 1.

Overview of study concepts for administration of Lactobacillus strains in AR. CFU, form and duration of administration, timing (in – or out of – allergen season), and additional medication are shown. CFU, colony-forming units.

Close modal

Lactobacillus species showed several effects on immunological parameters in allergic disease, but the exact mechanism is still unclear. Additionally, no specific Lactobacillus strain emerged as the most efficient one, and their modulatory effects seem to be strain-dependent. Since 11 of 14 human studies found significant effects of Lactobacillus strains on AR symptoms and no negative effects occurred, the treatment with probiotic bacteria seems to be suitable for AR patients. However, many parameters may influence the effect of probiotics, and therefore, a clear recommendation for a specific strain, and the dosage and timing of application is not yet possible. Further investigations and solid studies addressing mechanisms underlying the observed beneficial effects of probiotic treatments in rhinitis patients are required to make conclusive statements and to develop safe and less invasive or adjunctive therapies, respectively.

The authors have no conflicts of interest to declare.

The authors did not receive any funding.

N.C.S. and A.L. conceptualized the study and were involved in preparation and review of the manuscript.

Min YG. The pathophysiology, diagnosis and treatment of allergic rhinitis.
Allergy Asthma Immunol Res
. 2010;2(2):65.
Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008*: ARIA: 2008 update.
. 2008 Apr;63:8–160.
Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation.
. 2008 Jul;454(7203):445–54.
Canonica GW, Bousquet J, Mullol J, Scadding GK, Virchow JC. A survey of the burden of allergic rhinitis in Europe.
. 2007 Dec;62(s85):17–25.
Yamashita M, Matsumoto K, Matsumoto N, Kobatake E, Kabuki T. Anti-allergic effect of Lactobacillus helveticus SBT2171 on murine model of pollen allergy.
Funct Foods Health Dis
. 2019 Mar 29;9(3):166.
Peng GC, Hsu CH. The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite.
Pediatr Allergy Immunol
. 2005 Aug;16(5):433–8.
Probiotics in food:
health and nutritional properties and guidelines for evaluation
. Rome: Food and Agriculture Organization of the United Nations: World Health Organization; 2006. p. 50.(FAO food and nutrition paper).
Reid G, Anukam K, Koyama T. Probiotic products in Canada with clinical evidence: what can gastroenterologists recommend?
Can J Gastroenterol
. 2008;22(2):169–75.
World Gastroenterology Organisation. Probiotics and prebiotics [Internet]. 2008 [cited 2020 Mar 27];33–42. Available from:
Matsuzaki T, Chin J. Modulating immune responses with probiotic bacteria.
Immunol Cell Biol
. 2000 Feb;78(1):67–73.
Fujiwara D, Wakabayashi H, Watanabe H, Nishida S, Iino H. A double-blind trial of Lactobacillus paracasei strain KW3110 administration for immunomodulation in patients with pollen allergy.
Allergol Int
. 2005;54(1):143–9.
Singh A, Hacini-Rachinel F, Gosoniu ML, Bourdeau T, Holvoet S, Doucet-Ladeveze R, et al. Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial.
Eur J Clin Nutr
. 2013 Feb;67(2):161–7.
Ishida Y, Nakamura F, Kanzato H, Sawada D, Hirata H, Nishimura A, et al. Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis: a double-blind, placebo-controlled study.
J Dairy Sci
. 2005 Feb;88(2):527–33.
Wassenberg J, Nutten S, Audran R, Barbier N, Aubert V, Moulin J, et al. Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis: effect of L. paracasei strain on allergic rhinitis.
Clin Exp Allergy
. 2011 Apr;41(4):565–73.
Ivory K, Wilson AM, Sankaran P, Westwood M, McCarville J, Brockwell C, et al. Oral delivery of a probiotic induced changes at the nasal mucosa of seasonal allergic rhinitis subjects after local allergen challenge: a randomised clinical trial.
PLoS One
. 2013;8(11):e78650.
Nembrini C, Singh A, De Castro CA, Mercenier A, Nutten S. Oral administration of Lactobacillus paracasei NCC 2461 for the modulation of grass pollen allergic rhinitis: a randomized, placebo-controlled study during the pollen season.
Clin Transl Allergy
. 2015 Dec;5(1):41.
Perrin Y, Nutten S, Audran R, Berger B, Bibiloni R, Wassenberg J, et al. Comparison of two oral probiotic preparations in a randomized crossover trial highlights a potentially beneficial effect of Lactobacillus paracasei NCC2461 in patients with allergic rhinitis.
Clin Transl Allergy
. 2014;4(1):1.
Costa DJ, Marteau P, Amouyal M, Poulsen LK, Hamelmann E, Cazaubiel M, et al. Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN Study).
Eur J Clin Nutr
. 2014 May;68(5):602–7.
Helin T, Haahtela S, Haahtela T. No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC 53103), on birch-pollen allergy: a placebo-controlled double-blind study.
. 2002 Mar;57(3):243–6.
Lin W-Y, Fu L-S, Lin H-K, Shen C-Y, Chen Y-J. Evaluation of the effect of Lactobacillus paracasei (HF.A00232) in children (6–13 years old) with perennial allergic rhinitis: a 12-week, double-blind, randomized, placebo-controlled study.
Pediatr Neonatol
. 2014 Jun;55(3):181–8.
Giovannini M, Agostoni C, Riva E, Salvini F, Ruscitto A, Zuccotti GV, et al. A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis.
Pediatr Res
. 2007 Aug;62(2):215–20.
Martínez-Cañavate A, Sierra S, Lara-Villoslada F, Romero J, Maldonado J, Boza J, et al. A probiotic dairy product containing L. gasseri CECT5714 and L. coryniformis CECT5711 induces immunological changes in children suffering from allergy.
Pediatr Allergy Immunol
. 2009 Sep;20(6):592–600.
Ouwehand AC, Nermes M, Collado MC, Rautonen N, Salminen S, Isolauri E. Specific probiotics alleviate allergic rhinitis during the birch pollen season.
World J Gastroenterol
. 2009 Jul 14;15(26):3261–8.
Ahmed M, Billoo AG, Iqbal K. Efficacy of probiotic in perennial allergic rhinitis under five year children: a randomized controlled trial.
Pak J Med Sci
. 2019 Oct 5 [cited 2020 Apr 24];35(6):1538–43. Available from:
Wang X, Hui Y, Zhao L, Hao Y, Guo H, Ren F. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma.
PLoS One
. 2017;12(2):e0171721.
Wickens K, Barthow C, Mitchell EA, Kang J, van Zyl N, Purdie G, et al. Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years.
Pediatr Allergy Immunol
. 2018 Dec;29(8):808–14.
Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial.
. 2001 Apr;357(9262):1076–9.
de Moreno de LeBlanc A, Galdeano CM, Chaves S, Perdigón G. Oral administration of L. Casei CRL 431 increases immunity in bronchus and mammary glands.
Eur J Inflamm
. 2005 Jan;3(1):23–8.
Schabussova I, Hufnagl K, Wild C, Nutten S, Zuercher AW, Mercenier A, et al. Distinctive anti-allergy properties of two probiotic bacterial strains in a mouse model of allergic poly-sensitization.
. 2011 Feb 24;29(10):1981–90.
Pascal M, Perez-Gordo M, Caballero T, Escribese MM, Lopez Longo MN, Luengo O, et al. Microbiome and allergic diseases.
Front Immunol
. 2018;9:1584.
Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World allergy organization-McMaster university guidelines for allergic disease prevention (GLAD-P): probiotics.
World Allergy Organ J
. 2015;8(1):4.
Sunada Y, Nakamura S, Kamei C. Effects of Lactobacillus acidophilus strain L-55 on experimental allergic rhinitis in BALB/c mice.
Biol Pharm Bull
. 2007 Nov;30(11):2163–6.
Kay AB. Allergy and allergic diseases. First of two parts.
N Engl J Med
. 2001 Jan 4;344(1):30–7.
König K, Klemens C, Eder K, San Nicoló M, Becker S, Kramer MF, et al. Cytokine profiles in nasal fluid of patients with seasonal or persistent allergic rhinitis.
Allergy Asthma Clin Immunol
. 2015 Sep 22 [cited 2020 May 1];11(1). Available from:
Makino T, Yamashita M, Takeuchi N, Kabuki T, Hattori M, Yoshida T. Lactobacillus helveticus SBT2171 alleviates allergic symptoms in a murine model for pollen allergy.
Biosci Biotechnol Biochem
. 2019 Dec 2;83(12):2298–306.
Choi SP, Oh HN, Choi CY, Ahn H, Yun HS, Chung YM, et al. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice.
J Appl Microbiol
. 2018 Mar;124(3):821–8.
Repa A, Grangette C, Daniel C, Hochreiter R, Hoffmann-Sommergruber K, Thalhamer J, et al. Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy.
. 2003 Dec;22(1):87–95.
Hisbergues M, Magi M, Rigaux P, Steuve J, Garcia L, Goudercourt D, et al. In vivo and in vitro immunomodulation of Der p 1 allergen-specific response by Lactobacillus plantarum bacteria.
Clin Exp Allergy
. 2007 Sep;37(9):1286–95.
Tobita K, Yanaka H, Otani H. Anti-allergic effects of Lactobacillus crispatus KT-11 strain on ovalbumin-sensitized BALB/c mice.
Anim Sci J
. 2010 Dec;81(6):699–705.
Kim JY, Choi YO, Kwon JH, Ahn KM, Park MS, Ji GE. Clinical effects of probiotics are associated with increased transforming growth factor-β responses in infants with high-risk allergy.
J Korean Soc Appl Biol Chem
. 2011 Dec;54(6):944–8.
Ivory K, Chambers SJ, Pin C, Prieto E, Arqués JL, Nicoletti C. Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis.
Clin Exp Allergy
. 2008 Aug;38(8):1282–9.
Pochard P, Gosset P, Grangette C, Andre C, Tonnel AB, Pestel J, et al. Lactic acid bacteria inhibit TH2 cytokine production by mononuclear cells from allergic patients.
J Allergy Clin Immunol
. 2002 Oct;110(4):617–23.
Fujiwara D, Inoue S, Wakabayashi H, Fujii T. The anti-allergic effects of lactic acid bacteria are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance.
Int Arch Allergy Immunol
. 2004;135(3):205–15.
Daniel C, Repa A, Wild C, Pollak A, Pot B, Breiteneder H, et al. Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.
. 2006 Jul;61(7):812–9.
Charng YC, Lin CC, Hsu CH. Inhibition of allergen-induced airway inflammation and hyperreactivity by recombinant lactic-acid bacteria.
. 2006 Aug 14;24(33–34):5931–6.
Snel J, Vissers YM, Smit BA, Jongen JM, van der Meulen ET, Zwijsen R, et al. Strain-specific immunomodulatory effects of Lactobacillus plantarum strains on birch-pollen-allergic subjects out of season.
Clin Exp Allergy
. 2011 Feb;41(2):232–42.
Velez EM, Maldonado Galdeano C, Carmuega E, Weill R, Bibas Bonet ME, Perdigón G. Probiotic fermented milk consumption modulates the allergic process induced by ovoalbumin in mice.
Br J Nutr
. 2015 Aug 28;114(4):566–76.
Wachholz PA, Soni NK, Till SJ, Durham SR. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy.
J Allergy Clin Immunol
. 2003 Nov 1;112(5):915–22.
Holgate ST, Polosa R. Treatment strategies for allergy and asthma.
Nat Rev Immunol
. 2008 Mar;8(3):218–30.
Kim WG, Kang GD, Kim HI, Han MJ, Kim DH. Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 alleviate allergic rhinitis in mice by restoring Th2/Treg imbalance and gut microbiota disturbance.
Benef Microbes
. 2019 Feb 8;10(1):55–67.
Zhang J, Ma JY, Li QH, Su H, Sun X. Lactobacillus rhamnosus GG induced protective effect on allergic airway inflammation is associated with gut microbiota.
Cell Immunol
. 2018;332:77–84.
Mohamadzadeh M, Olson S, Kalina WV, Ruthel G, Demmin GL, Warfield KL, et al. Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization.
Proc Natl Acad Sci U S A
. 2005 Feb 22;102(8):2880–5.
Schabussova I, Hufnagl K, Tang ML, Hoflehner E, Wagner A, Loupal G, et al. Perinatal maternal administration of Lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy.
PLoS One
. 2012;7(7):e40271.
Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E, Perdigón G. Beneficial effects of probiotic consumption on the immune system.
Ann Nutr Metab
. 2019;74(2):115–24.
Sánchez B, Delgado S, Blanco-Míguez A, Lourenço A, Gueimonde M, Margolles A. Probiotics, gut microbiota, and their influence on host health and disease.
Mol Nutr Food Res
. 2017 Jan;61(1):1600240.
Tiihonen K, Suomalainen T, Tynkkynen S, Rautonen N. Effect of prebiotic supplementation on a probiotic bacteria mixture: comparison between a rat model and clinical trials.
Br J Nutr
. 2008 Apr;99(4):826–31.
Oozeer R, Leplingard A, Mater DD, Mogenet A, Michelin R, Seksek I, et al. Survival of Lactobacillus casei in the human digestive tract after consumption of fermented milk.
Appl Environ Microbiol
. 2006 Aug;72(8):5615–7.
Elli M, Callegari ML, Ferrari S, Bessi E, Cattivelli D, Soldi S, et al. Survival of yogurt bacteria in the human gut.
Appl Environ Microbiol
. 2006 Jul;72(7):5113–7.
Kechagia M, Basoulis D, Konstantopoulou S, Dimitriadi D, Gyftopoulou K, Skarmoutsou N, et al. Health benefits of probiotics: a review.
. 2013;2013:481651–7.
Wang MF, Lin HC, Wang YY, Hsu CH. Treatment of perennial allergic rhinitis with lactic acid bacteria.
Pediatr Allergy Immunol
. 2004 Apr;15(2):152–8.
Aldinucci C, Bellussi L, Monciatti G, Passàli GC, Salerni L, Passàli D, et al. Effects of dietary yoghurt on immunological and clinical parameters of rhinopathic patients.
Eur J Clin Nutr
. 2002 Dec;56(12):1155–61.
Del Piano M, Carmagnola S, Andorno S, Pagliarulo M, Tari R, Mogna L, et al. Evaluation of the intestinal colonization by microencapsulated probiotic bacteria in comparison with the same uncoated strains.
J Clin Gastroenterol
. 2010 Sep;44(Suppl 1):S42–6.
Singh M, Ranjan Das R. Probiotics for allergic respiratory diseases: putting it into perspective.
Pediatr Allergy Immunol
. 2010 Mar;21(2 Pt 2):e368–76.
Ishida Y, Nakamura F, Kanzato H, Sawada D, Yamamoto N, Kagata H, et al. Effect of milk fermented with Lactobacillus acidophilus strain L-92 on symptoms of Japanese cedar pollen allergy: a randomized placebo-controlled trial.
Biosci Biotechnol Biochem
. 2005 Sep;69(9):1652–60.
Willing BP, Russell SL, Finlay BB. Shifting the balance: antibiotic effects on host-microbiota mutualism.
Nat Rev Microbiol
. 2011 Apr;9(4):233–43.
Minic R, Gavrovic-Jankulovic M, Petrusic V, Zivkovic I, Eijsink VG, Dimitrijevic L, et al. Effects of orally applied Fes p1-displaying L. plantarum WCFS1 on Fes p1 induced allergy in mice.
J Biotechnol
. 2015 Apr 10;199:23–8.

Additional information

Edited by: H.-U. Simon, Bern.

Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.