INTRODUCTION:

Allergic rhinitis is a symptomatic disorder of the nasal passages, induced by a hyper-activation of the immune system towards allergens present in the air, resulting in a response mediated by IgE¹ immunoglobulins. Signs and symptoms of this condition may include runny nose with watery nasal discharge associated with nasal congestion, sneezing, itchy nose and palate, itchy ears and eye inflammation². Based on the time of year in which the symptoms appear, the following forms of pollinosis^3-6 can be distinguished, caused precisely by exposure to different types of pollen: early or pre-spring (due to sensitization to arboreal plants such as Cupressaceae, Betulaceae, Corylaceae), spring or spring-summer (due to sensitization to Graminaceae, Parietaria spp., Oleaceae), summer-autumn, rarer (due to sensitization to Compositae, Ambrosia spp.).

This pathology can lead to sleep disturbances, fatigue, depressed mood and cognitive impairment compromising the quality of life. Patients with allergic rhinitis can also develop sinusitis, nasal polyps and ear infections⁷. Triggers can be traced to household allergens such as mites and insects or external plant-based allergens, including pollen and mold. Various substances such as latex, tobacco smoke, exhaust gases and nitric oxide are additional triggers for allergic rhinitis⁸; the prevalence of this pathology is estimated at around 10-30% of the world population.

In recent years, a strong interest has arisen between the interaction of the intestinal microbiota with numerous diseases and several articles have been proposed that included clinical trials relating to the administration of prebiotic strains in the prevention and treatment of various acute and chronic diseases including allergic rhinitis.

The possible mechanisms responsible for the improvement of the symptoms of allergic rhinitis by probiotics⁹ have not yet been fully identified, however several authors^10,11 have hypothesized that the probiotic strains have the ability to alter the composition of the gut microbiota by modifying the host's immune system. These immunomodulatory effects have been recognized in cell culture models in which specific probiotic strains are present showing suppressive capacity towards T helper 2 limphocytes by modulating the TH1/TH2^12,13 ratio, stimulation of Toll-like receptor¹⁴ receptors and immunosuppressive regulatory T cells¹⁵.

MATERIALS AND METHODS:

The analysis of the literature for the elaboration of the systematic review was conducted in the Pubmed and Medline databases using review criteria based on the PRISMA statement guidelines drawn up by the Ottawa Hospital Research Institute for the review of the systematic reviews with the latest update¹⁶ and Jadad scale for reporting randomized controlled trials for the evaluation of selected clinical trials¹⁷.

The objective of this review is the evaluation of the integration of different species of probiotic strains as adjuvant therapy in the treatment of allergic rhinitis, in the reduction of associated symptoms (rhinorrhea, nasal itching, sneezing, nasal congestion, nasal obstruction, hyposmia, ocular itching and redness , lacrimation and eyelid edema), inflammatory indices and modulation of the immune system.

The inclusion criteria adopted were: subjects suffering from allergic rhinitis infection in adjuvant treatment with probiotic strains, age ≥19 years and articles available in full text; all items that did not meet these characteristics were excluded.

This bibliographic search has considered the data available on the Pubmed-Medline search engine using as keywords: probiotics, allergic rhinitis, with the following search criteria: ("probiotic s" [All Fields] OR "probiotical" [All Fields] OR "probiotics" [MeSH Terms] OR "probiotics" [All Fields] OR "probiotic" [All Fields]) AND ("rhinitis, allergic" [MeSH Terms] OR ("rhinitis" [All Fields] AND "allergic "[All Fields]) OR" allergic rhinitis "[All Fields] OR (" allergic "[All Fields] AND" rhinitis "[All Fields]))

Initially 51 initial results emerged, subsequently after evaluation of the abstracts 35 were selected and, after reading the full-text, 16 articles were considered eligible for our review (Figure 1).

Figure 1: Review process (PRISMA flowchart)

RESULTS:

This literature review analyzed a total of 16 literature articles available in the Pubmed-Medline database divided into 15 RCT studies and 1 systematic review. In order to facilitate the presentation of the results, the evaluation of the various clinical trials will be divided according to the species of probiotic strain analyzed.

Lactobacillus Rhamnosus GG®

Lactobacillus rhamnosus GG (LGG ®) is a probiotic strain characterized by a high survival rate through gastric juices, with good adhesion to intestinal epithelial cells^18,19. The Lactobacillus rhamnosus GG ® strain also stimulates the proliferation of intestinal epithelial cells and improves the secretion of protective mucins that protect the integrity of the intestinal epithelium, thus making it more "resistant" to the effects of pathogens, antibiotics and factors deriving from a diet unbalanced²⁰.

This probiotic strain is also known primarily for its ability to boost and support immune function and its positive effects on digestion^21,22,23.

Three studies in this review were able to evaluate the possible beneficial effects of Lactobacillus rhamnosus GG in the prevention and treatment of allergic rhinitis symptoms and in modulating the immune system.

The first study²⁴ enrolled 38 patients, all with a known allergy to birch pollen, and divided them into two equal groups of 19, a treatment group and a control group. Participants in both groups began taking a supplement five and a half months before the birch pollen season began; those in the treatment group received a supplement containing LGG ® and those in the control group received a placebo. The results showed that, after 5 months of supplementation, increased levels of IgA specific for salivary allergens were observed in the probiotic treatment group. The authors concluded that LGG ® showed immunostimulating effects in the oral mucosa and that taking a probiotic can help support allergic symptoms.

In another double-blind RCT study²⁵, 39 patients were given L. Rhamnosus 1 million CFU for 4 weeks and 38 patients were given placebo; all participants had allergic rhinitis. There were improvements in the treatment group from the point of view of clinical symptoms at 4 weeks (measurement with SNOT20 validated questionnaire), but these effects tended to decrease after 4 weeks from the end of administration.

In the last RCT analyzed²⁶, again conducted in a double-blind manner on a sample of 139 athletes, with the aim of evaluating the antibody and immune response, 2 billion CFU and the control group consisting of 2 billion CFU were administered to a group of 69 subjects. 70 placebo athletes. The authors found no significant differences after 3 months of treatment in serum IgE, eosinophils and serum ECP values.

Lactobacillus Gasseri:

Several studies have shown that L. Gasseri is able to attenuate asthma symptoms in the pediatric population, modulate the inflammatory response in the airways, also showing a suppression of the infiltration of TH17 lymphocytes in the lung²⁷.

From the data analyzed in the literature we found three articles, two RCTs and a clinical trial conducted a few weeks before the allergic season.

In the first clinical trial analyzed²⁸ the study group was given a milk-based drink supplemented with L. Gasseri (1.4 × 108 cfu/ml) and L rhamnosus (1.0 × 107), while the control group was given fermented milk only. The purpose of this RCT was to evaluate at the start of the study, at 6 and 10 weeks nasal, ocular and respiratory symptoms as well as an evaluation of IgE, TH1/TH2, chemokines (TARC) and CRP in the two study groups, resulting in an improvement in the score. referable to symptoms, reduction of drug consumption and better modulation of IL-4, IL-5 and reduction of TH2 lymphocytes.

The second study²⁹ also shows results comparable to the previous one; in this trial 87 patients were enrolled in the group receiving the probiotic (L. Gasseri 1.2 billion CFU with a combination of bifidobacterium 0.3 billion CFU), while 86 patients in the group receiving a placebo drug. The authors concluded that after a period of 6 weeks the patients reported an improvement in clinical symptoms (evaluation by RQLQ questionnaire), increased probiotic strains in the stool, IgE unchanged between the two groups but with increased T reg lymphocytes in the group with probiotic.

In the latest trial³⁰, they used Lactobacillus gasseri fermented milk in 15 individuals with elevated serum IgE and allergic rhinitis, at a dose of 200ml/day for 4 weeks and observed a significant decrease (p <0.05) in total serum levels of IgE, as well as IgE specific for mites and Japanese cedar pollen, after 28 days of exposure compared to the baseline value with an increase in the number of TH1 cells.

Lactobacillus Plantarum:

In preliminary studies^31,32 L. plantarum has been shown to relieve the symptoms of allergic rhinitis in mice by recovering the Th1/Th2 balance through the enhancement of the Th121-type immune response.

In our review we found two RCT studies, which showed positive effects following the administration of L. Plantarum in patients with allergic rhinitis. In the first trial analyzed³³ the participants were university students divided into two treatment and placebo groups; the study was conducted in two different seasons, spring and autumn. Subjects who received the probiotic showed a reduction in the nasal symptom score questionnaire at the end of the study, an increase in Th1 lymphocytes, and a decrease in Th2 lymphocytes.

Another clinical trial evaluated³⁴ demonstrated a reduction in total nasal simptom score (TNSS), plasma IgE, improved ratio of IL-10 to IL-4, reduction in urinary levels of prostaglandin F2α and leukotriene E4 in the 47 subjects in the receiving group. the probiotic compared to the 48 who received the placebo.

Lactobacillus Paracasaei:

Several clinical studies involving the pediatric population have shown a clinical efficacy of L. Paracasaei in the symptoms associated with allergic rhinitis, improvement in the quality of life and improvement of immunity³⁵.

In a Japanese study³⁶ the daily intake of L. Paracasaei in patients with cedar pollinosis was studied in 126 patients who received the probiotic strain or a placebo in a double-blind study. The study started 1 month before the start of the pollen season and lasted 3 months. A significant reduction in nasal symptoms and serum eosinophilic cation protein level and improvement in quality of life scores occurred in patients who received L. Paracasaei.

In another trial³⁷ he enrolled 31 patients (16 probiotic group and 15 placebo group) demonstrating that after 4 weeks in the group treated with L. Paracasaei, nasal symptoms (NPT) had improved and there was a reduction in IL-5 and IgG4. Another RCT³⁸ of particular interest as it enrolled a large number of patients (602) who began the trial phase taking antihistamines for 10 days and were subsequently divided into an antihistamine group with probiotic and an antihistamine group with placebo for 15 days after which they continued the treatment without the antihistamine until reaching the fifth week. Subjects enrolled in the group taking L Paracasaei showed an improvement in quality of life (RQLQ questionnaire), improvement in ocular symptoms but not nasal ones.

Lactobacillus Acydophilus and Bifidobacterium Lactis:

Animal studies have suggested that L. Acycophilus is able to reduce several allergic diseases, in our review we have analyzed several RCTs and clinical trials that have shown relative efficacy of this probiotic, alone or in combination with other strains in the treatment of allergic rhinitis.

In a randomized, double-blind, placebo-controlled clinical trial³⁹, 49 patients with allergic rhinitis were randomized to receive 100 ml of heat-treated fermented milk containing L-92 (n = 25) or acidified milk without lactic bacteria (placebo; n = 24) for 8 weeks. Symptom severity was assessed based on changes in scores at 8 and 8 weeks demonstrating improvement in nasal and ocular symptoms; IgE and TH1 / TH2 ratio remained unchanged between the two groups.

An RCT⁴⁰ study involving the administration of B. Lactis NCC 2818 (4 billion CFU) for 8 weeks showed improvement in nasal symptoms (TNSS questionnaire) and reduction of TH2, IL- lymphocytes in the probiotic treatment group (10 patients). 4 and IL-5, CD63 basophils compared to 10 placebo-treated patients.

Two other studies, a clinical trial⁴¹ and an RCT⁴² demonstrated a reduction in symptoms and an improvement in quality of life (RQLQ questionnaire), a reduction in total IgE and a better TH1 / TH2 ratio in the group of patients treated with L. Acydophilus in combination with others. 5 bacterial strains (®AlergyCare Probiotik).

The last two studies considered, both RCTs involved the administration of L. Acydophilus in combination with Bif. Lactis; the first study⁴³ concluded that patients in the group treated with this combination added to 3 jars of Yogurt (®Parmalat Kyr) showed improvement in symptoms, increased interferon gamma and decreased IL-4, other parameters such as IgE and cytokines were unchanged from the control groups (unfermented yogurt and placebo). In the second RCT⁴⁴ study, they concluded that the 52-patient treatment group receiving the probiotic combination (®Pollagen) showed decreased symptom score and decreased inflammatory indices.

Lactobacillus Casei Shirota:

Similarly to other probiotic strains L. Casei Shirota has shown relative efficacy in the treatment of allergic rhinitis in animal experiments.

In this review of the literature we found two articles that analyzed the effectiveness of this probiotic strain in the prevention and treatment of symptoms of allergic rhinitis and on the modification of immune and inflammatory indices.

The first RCT⁴⁵ study, in Japanese cedar pollinosis, which ended after 8 weeks concluded that the group treated with fermented milk containing LcS does not prevent allergic symptoms in patients with allergic rhinitis, but may delay the occurrence of allergic symptoms in patients with symptom scores. moderate to severe nasal passages. In the second RCT analyzed⁴⁶, lasting 5 weeks, a group of 10 patients received the probiotic, while the second group, also of 10 patients, received placebo; at the end of the trial the patients who had received L. Casei Shirota showed a reduction in allergic symptoms and a reduction in specific IL-5, IL-6 IgE and IgG.

Bifidobacterium Longum:

Two studies^47,48, demonstrated the efficacy of B. Longum by reducing the serum levels of ovalbumin specific immunoglobulin E (OVA), improving the IgG2a / IgG1 ratio specific for OVA, in a mouse model; furthermore, stimulation of B lymphocyte proliferation and production of interleukin-12 (IL-12) in J774.1 cells similar to macrophages has been demonstrated in vitro.

A randomized, double-blind, placebo-controlled trial⁴⁹, 44 subjects with allergic rhinitis received BB536 or placebo for 13 weeks during pollen season. The probiotic-treated group experienced significant reductions in rhinorrhea, nasal blockage, and decreased TH2 lymphocytes and plasma IgE compared with the placebo group.

In another study⁵⁰, lasting 14 weeks, a total of 40 subjects were divided into a treatment group supplemented with B. Longum BB0356 and a control group administered only yogurt; at the end of the study according to the criteria of the Nasal Allergic Clinic, the patients in the probiotic group showed a reduction in nasal and ocular symptoms, a reduction in specific IgE, a better TH1 / TH2 ratio, an increase in IL-10 and a reduction in eosinophils.

Bacillus Clausii:

A single study was found in the literature regarding the administration of B Clausii in adult patients with allergic rhinitis.

In this clinical trial⁵¹, B. Clausii was administered for 4 weeks to 10 subjects with allergic rhinitis, concluding that this probiotic exerts an immunomodulatory activity by affecting cytokines (reduction of IL-4 and increase of TGF beta, IL-10) to confirmation of data from previous studies performed in pediatric subjects.

Clostrydium butirricum:

A randomized controlled clinical trial⁵² evaluated the administration of C butirricum as adjuvant to immunotherapy (SIT). The participants were divided into 4 groups: SIT, SIT + C. Butirricum, only C. butirricum and placebo; this study lasted 6 months and patients were evaluated with nasal symptom score (NSS) and blood assessment for IgE TH2 and SPT index. The authors concluded that the association between C. Butirricum and SIT reduced symptoms by 81.2% compared to SIT alone (52.5%), furthermore this combination reduced the NSS score, drug consumption, IgE, TH2 lymphocytes. .

The action of this probiotic would seem to be due to the butyrate which is able to block the histione deacetylase-1 promoter of IgE production in antigen-specific beta cells.

CONCLUSIONS:

Allergic rhinitis is a disease in constant increase in the world population, with an estimated prevalence of 20-30%; the search for new treatment alternatives that could improve patients' quality of life could be represented by probiotics. Most of the studies analyzed showed that probiotics promote an improvement in symptom control and quality of life, a better modulation of the immune response⁵³ and a positive action on the intestinal microflora. However, it must be considered that the scientific articles evaluated sometimes present considerable differences in treatment and this heterogenicity could be a possible source of bias or confusion in the results of our article.

The data presented are also confirmed by a further review of the literature⁵⁴ which evaluated 23 studies on 1919 patients. Concluding that supplementation with probiotics is able to improve the quality of life (QRLQ score) and reduce plasma IgE compared to subjects treated with placebo or different therapy; the authors however concluded that further studies are necessary in order to implement probiotic therapy as an adjuvant treatment in the treatment of allergic rhinitis

The present review of the literature has been able to demonstrate that different probiotic strains could show a positive efficacy in the prevention and treatment of allergic rhinitis, but in order to be able to reach a definitive conclusion, further research would be necessary to seek the selection of a probiotic strain. more effective and safe, dosage and timing of integration; furthermore, clinical trials would be needed to enroll larger samples of patients and to identify the mechanisms of action of probiotics responsible for modulating the immune response in this pathology.

SOURCE OF FUNDING:

The authors declare that there are no sources of funding, neither from internal bodies nor external bodies.

CONFLICT OF INTEREST:

The authors declare the absence of any kind of conflict of interest.

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Received on 27.07.2022 Modified on 22.08.2022

Research J. Pharm. and Tech 2023; 16(5):2393-2398.

DOI: 10.52711/0974-360X.2023.00394