Next Article in Journal
Comparing the Rate-All-That-Apply and Rate-All-Statements Question Formats across Five Countries
Next Article in Special Issue
Characterization and Determination of Nanoparticles in Commercial Processed Foods
Previous Article in Journal
Hydrogen Peroxide Effects on Natural-Sourced Polysacchrides: Free Radical Formation/Production, Degradation Process, and Reaction Mechanism—A Critical Synopsis
Previous Article in Special Issue
Elevated Concentrations of Metal(loids) in Seaweed and the Concomitant Exposure to Humans
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

Probiotics as a Possible Strategy for the Prevention and Treatment of Allergies. A Narrative Review

Aroa Lopez-Santamarina
Esther Gonzalez Gonzalez
Alexandre Lamas
Alicia del Carmen Mondragon
Patricia Regal
Jose Manuel Miranda
Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain
Author to whom correspondence should be addressed.
Foods 2021, 10(4), 701;
Submission received: 17 February 2021 / Revised: 22 March 2021 / Accepted: 23 March 2021 / Published: 25 March 2021
(This article belongs to the Special Issue Foods: New Perspectives)


Allergies are an increasing global public health concern, especially for children and people living in urban environments. Allergies impair the quality of life of those who suffer from them, and for this reason, alternatives for the treatment of allergic diseases or reduction in their symptoms are being sought. The main objective of this study was to compile the studies carried out on probiotics as a possible therapy for allergies. The most studied allergies on which probiotics have been shown to have a beneficial effect are rhinitis, asthma, and atopic dermatitis. Most studies have studied the administration of Lactobacillus and Bifidobacterium spp. in children and have shown beneficial effects, such as a reduction in hyperreactivity and inflammation caused by allergens and a decrease in cytokine release, among other beneficial effects. In the case of children, no clear beneficial effects were found in several studies, and the potential risk from the use of some opportunistic bacteria, such as probiotics, seems controversial. In the studies that reported beneficial results, these effects were found to make allergy symptoms less aggressive, thus reducing morbidity in allergy sufferers. The different effects of the same probiotic bacteria on different patients seem to reinforce the idea that the efficacy of probiotics is dependent on the microbial species or strain, its derived metabolites and byproducts, and the gut microbiota eubiosis of the patient. This study is relevant in the context of allergic diseases, as it provides a broader understanding of new alternatives for the treatment of allergies, both in children, who are the main sufferers, and adults, showing that probiotics, in some cases, reduce the symptoms and severity of such diseases.

1. Introduction

An allergy is defined as a hypersensitivity reaction caused by an immunological response to a specific antigen, known as an allergen. Allergens act on innate immune cells. Repeated contact with an allergen triggers the activation of mast cells and basophils and the release of allergic mediators, resulting in symptoms ranging from sneezing and itchy rashes to severe shortness of breath and anaphylaxis [1,2,3]. Currently, the list of allergic diseases published by the WHO includes asthma, rhinitis, conjunctivitis, rhinosinusitis, anaphylaxis, atopic eczema, hives, and angioedema, as well as secondary reactions caused by drugs, foods, or insects [4].
Today, approximately 1 billion people worldwide suffer from allergies, and these numbers are estimated to increase to 4 billion in the next 30–40 years [1]. In recent years, the prevalence of allergic diseases has increased greatly, to the point that 30–40% of the world’s population now suffers from one or more allergic diseases. It is important to note that these diseases affect all age groups, but they are more frequently reported in childhood [5].
While no determinant risk factors have been identified, it is possible that environmental factors, such as cigarette smoking, air pollution, and exposure to allergens explain the observed changes in the prevalence of allergic diseases [6]. A common explanation for the increased prevalence of allergic diseases is the “hygiene hypothesis”, first proposed in 1989 by Strachan [7], in which it is stated that a lack of exposure in childhood to infectious agents, symbiotic microorganisms, and parasites increases the child’s susceptibility to these diseases later in life [6]. Decreased microbial exposure due to improved hygiene, changes in diet, or increased use of antibiotics may be determinants of an increased prevalence of allergies [7,8,9]. Additionally, there is a lot of evidence suggesting that living in rural areas in childhood has a protective effect against allergic disease, such as atopy, allergic rhinitis, and asthma [10,11]. This may be related to environment-derived factors, such as contact with bacterial endotoxins [12], contact with animals [13], or intake of raw or lightly processed milk [13,14]. In recent decades, the migration from traditional farming to the urban environment, increase in processed food intake, lack of contact with animals, and excessive hygiene has been related to the increase in the incidence of allergic diseases [15,16].
Due to the increase in allergies, their prevention and treatment have become a global public health priority. For this reason, new alternatives are being sought, one of which could be the use of probiotics to prevent these diseases and reduce their symptoms [5]. “Probiotic” means “for life”, and probiotics are defined as “Live microorganisms that, when being administered in appropriate doses, confer a benefit to the health of the host” [5]. The use of probiotics to treat or prevent specific diseases is a branch of microbiology known as “therapeutic microbiology” [17,18,19,20]. Probiotics exert multiple health effects, such as immunomodulatory agents and activators of host defense pathways, which reduce morbidity [21]. In the context of allergic disease, the probiotics’ microbiome is essential for the development of host immune responses. Effective probiotics must be resistant to bile salts, gastric enzymes, and a low pH, and they cannot cause mucosal inflammation or infection [22].
The population of microorganisms that inhabits a determined ecological niche of healthy individuals is termed the intestinal microbiota. Its colonization begins before birth and matures slowly, until it reaches the adult state at around 3 years of age. The human gut microbiota establishes a symbiotic relationship with the host and plays a very important role in human health, because dysbiosis in the gut microbiota often occurs in the presence of disease [17,20]. The intestinal microbiota constitute a key factor in the development of an adequate immune response, because the contact between gut bacterial antigens and the part of the immune system associated with the intestine represents an important component of the human immune system [17]. The microbiota play a fundamental role in the development of the human immune system, especially in the first years of life. Its main role is to intervene in the homeostasis and immunity of the intestine [17].
The main objective of this study is to provide a literature review of the effects of the administration of probiotics in the prevention and treatment of allergic diseases. This study is relevant, because it broadens the knowledge of new alternatives for the treatment of these diseases in both children and adults, reduction in the symptoms associated with allergies, and prevention of the occurrence of allergen-caused acute adverse episodes.

2. Methodology

A narrative literature search was conducted up to 10 February 2021 for all the available literature in the following databases: Web of Science, PubMed, and Scopus. A combination of the following search terms was applied: “probiotics” and “allergic diseases”; “gut microbiota” and “allergic diseases”. The search terms were adjusted to the specific databases and consisted of a combination of free-text searches. The selection of articles will be limited to studies published in English and Spanish, with no restrictions on the year of publication, although the most prominent articles are those published after 2015. A total of 115 articles were selected and included in the review. The following data on the study characteristics were extracted from the included records: author and year of publication, type of study, probiotics used, dosage and time of administration, type of allergy, and the conclusions of each study. The authors reviewed the titles and the abstracts. If the abstracts reported the use of diaries that contained narrative elements, full texts were read, and if the pre-established eligibility criteria were met, they were included in the review. A narrative approach containing summary tables and graphs will facilitate the synthesis of the included studies.

3. Results and Discussion

3.1. Characteristics of Allergic Diseases and Most Common Allergic Diseases

In allergic diseases, there is a disturbance in the balance between T helper (Th)1 and Th2 lymphocytes in favor of Th2 lymphocytes. Th1 lymphocytes are key to infection, activating macrophages to defend the body primarily against intracellular microbes. Th2 lymphocytes, on the other hand, activate eosinophils and mast cells and induce the production of IgE, which is responsible for allergies. These allergies are caused by the response of an inappropriate immune response of Th2 lymphocytes to different antigens, including environmental or food antigens. The activation of this response leads to the secretion of interleukins (IL)-4, IL-5, and IL-13 and an allergen-specific IgE production, which drives allergic inflammation [1,10]. Interferon (INF)-γ inhibits Th1 activity by inducing these cytokine responses, thus maintaining an allergic phenotype [23].
The prevalence of allergic diseases has doubled in the industrialized parts of the world in the last 25 years [6]. These diseases mainly affect children and young people, but as they age, the severity and complexity of these diseases increase, resulting in an adverse impact on their quality life and high costs to the health care system [10,24]. In general terms, approximately 200–250 million people suffer from food allergies, one-tenth of the population suffers from drug allergies, and 400 million suffer from rhinitis [24]. Worldwide, 300 million people suffer from asthma, and this incidence is expected to increase by 100 million in 2025 [25]. Food allergies are recognized as the most common immune disorders [26], and they are considered a world health risk, particularly in developed countries [27]. The major risk factors for the development of food allergies are related to genetics, the environment, and immune tolerance failure. Additionally, gut microbiota composition and activity have an important role in immunological development, and thus, gut microbiota eubiosis is recognized a key factor in preventing food allergies [26,28].
One variable on which these allergic diseases depend is sex. Due to their characteristics and specific patterns in women, women are more susceptible than men to allergies due to the ovarian hormones and hyperreactivity of the airways, which may occur during the menstrual cycle or pregnancy [29,30]. Previous studies showed that a significant percentage of women with asthma suffer worse symptoms during the perimenstrual phase [31,32].
Allergic rhinitis (AR) is foremost among the most common allergic diseases. It affects between 10% and 20% of the total population and is therefore the most prevalent chronic non-communicable disease in the world [33]. However, the prevalence of this disease is probably underestimated because many patients do not recognize rhinitis as a disease and therefore do not seek medical advice [34]. The most important allergens that trigger AR are pollens. AR results from immunoglobulin (IgE)-mediated inflammation of the nasal mucosa, which is characterized by pruritus, sneezing, rhinorrhea, and nasal congestion. In addition, AR is a potential risk factor for asthma [24], another common allergic disease and chronic inflammatory disorder of the airways, which currently affects some 300 million people worldwide [24,35]. Asthma is a heterogeneous disease, in which inflammation of the airways occurs and respiratory symptoms, such as wheezing, chest tightness, and coughing, along with shortness of breath, which varies in duration and intensity [36].
Urticaria is a disorder with various underlying causes. It is estimated that approximately 25% of people experience at least one episode of urticaria in their lifetime, but only 3% will develop chronic urticaria [37]. It is characterized by the appearance of hives, lasting between 1 and 24 h, and/or angioedema, which can last up to 72 h [24]. The activation of mast cells located superficially in the skin leads to urticaria, while mast cells in the dermis are involved in angioedema. Histamine is the main mediator in urticaria and in many cases of angioedema [24,38].
The most common chronic inflammatory skin disease is atopic dermatitis (AD). The incidence of AD has increased 2- to 3-fold in recent years in industrialized countries [39,40]. In the last 30 years, the prevalence of this disease has increased to 10–20% in children and 1–3% in adults. This chronic inflammatory skin disease is also known as atopic eczema, is very pruritic, and is characterized by erythema and oedema. In addition, AD usually occurs during infancy and childhood [41]. AD may have a mixed IgE-mediated and non-IgE-mediated mechanism [10]. Atopy manifests as allergic rhinitis, bronchial asthma, atopic dermatitis, or even food allergies and is defined as the development of an immediate hypersensitivity reaction to environmental and food antigens due to a genetic predisposition [24,35]. A variant of AD is allergic contact dermatitis (ACD), which manifests due to a delayed hypersensitivity reaction and is mediated by T-cells in the skin. In this case, the allergens, which are called “haptens”, are of a low molecular weight and bind to proteins in the skin, where they become antigenic [42].
Food-origin allergies have a high morbidity, which affects the sufferer’s quality of life; involve high costs; and, in the case of anaphylaxis, can lead to death. Worldwide, 220–250 million people may suffer from food-origin allergies [43]. The foods most frequently implicated in pediatric patients are cow’s milk and eggs. Moreover, milk or egg sensitization in children is associated with an increased risk of developing dust mite allergy and even asthma. In many cases, food allergies are mediated by IgE [10]. In adulthood, the most common foods implicated in allergies are legumes, nuts, fruits, and crustaceans [43].
Anaphylaxis is the most serious allergic disease and can be fatal. The onset can be within minutes or even hours and usually affects different body systems. The triggers of anaphylaxis vary with age and geography, and the prevalence is at least 1% [44]. Anaphylaxis is usually IgE-mediated and can be due to food, insect venom, drugs, or latex [10].

3.2. The Immune System and Probiotics

The human intestinal microbiota constitutes a complex ecosystem that includes, in addition to bacteria, fungi, Archaea, viruses, and protozoa. The concentration of bacteria increases from the stomach the duodenum, but it is in the large intestine where it rises up to 1011–1012 UCF/g [45]. It has been estimated that there are at least 1800 genera and between 15,000 and 36,000 species of bacteria in the large intestine [17]. Firmicutes and Bacteroidetes are the main bacterial phyla, followed by Actinobacteria, Proteobacteria, and Verrucomicrobia. In addition, fungi and protozoa make up approximately 1% of the species in our gut microbiota [45,46].
“Probiotic” means “for life”, and probiotics are currently used to refer to bacteria that have beneficial effects on human and animal health [17]. In 2001, the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) defined them as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” [47]. This definition was corrected in 2014 by the International Scientific Association for Probiotics and Prebiotics, and it now reads “microorganisms for which there is scientific evidence of safety and efficacy” and excludes “live cultures associated with fermented foods for which there is no evidence of a health benefit” [48].
Probiotics contribute various beneficial effects on human health and are used to treat different infectious and non-infectious diseases. Various effects have been seen in the form of protection against infections, decreases in irritable bowel symptoms, the inhibition of Helicobacter pylori growth and viral infections [49], the prevention of cancer, decreases in gut inflammatory response, and the prevention and/or treatment of allergies, which is the focus of this review [5].
It is believed that the administration of beneficial microorganisms may be the key to improving health and susceptibility to disease, as human organisms and the gut microbiota establish a symbiotic relationship important for the maintenance of human health [17]. It is likely that these microbiota organisms have evolved along with our immune system, thus promoting immune tolerance. This includes the induction of regulatory T cells (Treg) and the control of Th2 and Th1 balance, which may prevent the development of allergic and autoimmune diseases [1].
Probiotics can stimulate the immune system compounds secreted or present in the cellular barrier. Therefore, probiotic use improves the body’s defenses by triggering an immune response, according to the pathological state, and promoting a balance between pro- and anti-inflammatory cytokines that are secreted by activated immune cells. Probiotics hence act as a non-specific adjuvant to the innate immune response [50]. There is evidence that probiotics promote the production of some cytokines, including IL-10, transforming growth factor (TGF)-β, IL-12, and INF-γ, which regulate the immune response and reduce allergic inflammation [10].
Many studies have shown that the gut microbiota and probiotic intake can support maturation of the immune system during the first years of life due to different physiological and metabolic reactions in the host. The most promising probiotics in terms of immune system development are those belonging to the genera Lactobacillus and Bifidobacterium [6]. The effects of probiotics are dose- and strain-dependent [51,52] and may be influenced by age-specific functions, such as the maturity of the host’s intestinal barrier. It was suggested that the perinatal period may represent a window of opportunity for effective probiotic intervention in allergic diseases [53]. In the first stage of life, the microbiota is still developing, so the administration of probiotics leads to a proper microbial colonization and results in a greater effectiveness in the prevention and treatment of different diseases [17]. The immune effects of probiotics, which are primarily mediated through the innate immune system, include the promotion of epithelial integrity, intestinal permeability, and mucus production through the production of anti-inflammatory cytokines and tolerogenic CD103+ dendritic cells, in addition to the promotion of the differentiation and proliferation of regulatory T cells, the inhibition of the Th2 cell response, and an increased release of IgA from plasma cells [54,55]. The therapeutic potential of probiotics in allergic diseases is mediated by various mechanisms of action, such as the modulation of the immune response, competitive inhibition of invasive flora in the gut, modification of pathogenic toxins and host products, and an increased epithelial barrier function [41].
Lactobacillus reduces proinflammatory responses by regulating nuclear factor kappa B (NF-κB) signaling. Probiotics also promote the maturation of dendritic cells (DCs) into anti-inflammatory cytokines, such as IL-10. In addition, human monocyte-derived DCs can release IL-10 when treated with probiotics, thus triggering the differentiation and survival of Tregs [23]. Bifidobacterium animalis and Bifidobacterium longum induce the release of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) by DCs, while only Bifidobacterium bifidum can activate Th17 cells through the release of IL-17. Different studies have indicated that probiotics can modulate the Th1/Th2 balance and, consequently, prevent inflammatory diseases, such as allergies [23].

3.3. Use of Probiotics in Allergic Diseases

The increased prevalence of allergies, such as eczema, may be due to alterations in the gut microbiota in early life, such as a reduced abundance of the Proteobacteria phylum and the general Bifidobacterium, Akkermansia, Faecalibacterium, and Lachnospira [52,56]. For example, an association has been described between gut colonization with Clostridium difficile and allergies in children. Various studies have shown that children with atopic dermatitis have a less diverse gut microbiota [56,57] and lower Bifidobacterium levels [57] than healthy children. In allergic children, higher counts of Staphylococcus aureus and Enterobacteriaceae and lower Bifidobacterium counts were found than in healthy children [58]. In addition, a lower colonization of enterococci during the first month of life and of Bifidobacterium during the first year of life have been found in infants with allergies, compared to non-allergic infants [58].
It has been proposed that probiotics could potentially restore intestinal homeostasis and prevent or alleviate allergies by interacting with the intestinal immune cells [51]. Moreover, symbiotics, which are a synergistic combination of probiotics and prebiotics, have proven beneficial for different allergic conditions, for example, by reducing asthma-like symptoms and the use of asthma medications [59].
Probiotics are useful for the modulation of allergic diseases, as they stimulate the levels of IgA in the mucosa and the T and B cells of the immune system [23]. The results of different studies examining the influence of probiotics on allergic diseases have been contradictory, and as a result, few practical recommendations as to the use of probiotics in allergic diseases have been established [60]. It is important to note that, due to multiple factors, the results vary between studies (Figure 1). The impact of probiotics on humans is highly variable between individuals. For example, a recent study found that individuals with a healthier gut microbiota composition responded in a better way than other individuals to the administration of probiotics [61]. This result is logical, because the action of probiotics depends on several factors, including colonization resistance, acid and short chain fatty acid production, the competitive exclusion of pathogens, and bacteriocin production, which can influence probiotic persistence [62,63]. Zmora et al. [64] demonstrated that persistent personalized gut mucosal resistance to commercial probiotics is associated with unique host and microbiome features. For example, a probiotic’s colonization can be affected by an under-representation of specific carbohydrate-utilization genes in the gut, thus preventing the complex metabolization of polysaccharides by the probiotic bacteria [62]. Thus, the efficacy of probiotics is dependent on both the microbial species or strain and its derived metabolites and byproducts (commonly named as postbiotics), as well as the number of probiotic cells and type of probiotic carrier [27].
Previous studies have found that supplementation with various probiotic preparations can balance the intestinal microbiota, regulate the immune system, and reduce allergies. Further, these studies have explored new strains of probiotics, probiotic genomic characteristics, and the in vivo mechanisms of action, formulation processes, and safety of probiotics [65,66]. Currently, studies are attempting to identify protective factors that regulate the immune system and allow for tolerance of different allergens in a specific way. One of the most studied probiotics is Lactobacillus GG, which is frequently studied in connection with the management of AD, although the results have been quite inconsistent [8]. Further, Lactobacillus were able to reduce allergic symptoms and to reduce morbidity in children [67].
Taniuchi et al. [68] demonstrated that a Bifidobacterium species was effective in the treatment of cow’s milk hypersensitivity in infants with atopic dermatitis. In addition, Enomoto et al. [69] demonstrated that prenatal and postnatal supplementation with two species of Bifidobacterium reduced the risk of developing eczema and atopic dermatitis in infants. These differences disappeared at 10 months of age, highlighting that the early stage microbiota is particularly important for regulating allergies in children.
Two systematic reviews and meta-analyses show that probiotic supplementation before and after birth can prevent allergic diseases, particularly eczema [70,71]. On the other hand, when probiotics are administered only after birth, they may not be effective in preventing allergic diseases [71,72].
Many animal studies, mainly in mice, in which different probiotics in isolation or mixtures of them were used to treat or prevent allergic diseases, show an effect. Obviously, experimental animals differ widely from humans in key aspects, such as the gut microbiota composition, immune function, or metabolism [45]. Thus, extrapolating the results obtained from animal models to humans may not be valid and should always be considered as preliminary or limited.
The probiotics most often used in these studies are the Lactobacillus and Bifidobacterium genera and, to a lesser extent, Enterococcus [73]. The use of Enterococcus as probiotics presents some intrinsic risks that makes them poorly suited to use as probiotics, especially the E. faecium and E. faecalis species. As opportunistic pathogens, both enterococci possess an array of virulence factors and antibiotic resistance determinants, which render them controversial. Even in avirulent enterococci, when they reach the intestinal tract, they can interact with endogenous enterococci and other commensals that could lead to bi-directional genetic exchange [65,66].
In terms of allergies, the most studied are those related to the airways, such as asthma, but also atopic dermatitis [74,75] and food allergies [6,76]. The beneficial effects of probiotics on allergies include a reduction in hyperreactivity and inflammation due to the presence of allergens, a decrease in interleukins and eosinophils, and a reduction in TNF and INF, etc.
In addition to the animal studies, there have also been many studies with humans, especially children (Table 1). As in the studies with mice, in this case, the probiotics most often used were of the genera Bifidobacterium and Lactobacillus, or mixtures of them. To a lesser extent, Propionibacterium [77] or Escherichia coli and Enterococcus faecalis [8] were used, and these probiotics were administered in doses of 107 to 1010 colony-forming units (CFU)/day. Today, the consensus statements consider a number of viable cells of 1 × 109 CFU/day in food and food supplements as the minimum number to be effective [48]. To a lesser extent, food and respiratory allergies have been studied. The beneficial effects found in these studies were a reduction in inflammatory cells, decrease in interleukins, reduction in TNF and INF, and, above all, reduction in symptoms and improvement in the quality of life of people suffering from these allergies. Researchers, such as Simpson et al. [78] and Loo et al. [79], followed up their studies for several years to observe the effects of probiotics over time. Studies with a follow-up of 5 years or longer show that the greatest protective effect of probiotics against AD occurs in early childhood and that this effect is less likely to be sustained until school age [78].
As shown in (Table 1), most studies employed Lactobacillus or Bifidobacterium spp. as the probiotics. However, other bacterial species were also employed, such as Propionibacterium freudereichii ssp shermanii JS [77], Escherichia coli DSM 17252, and Enterococcus faecalis DSM 1644 [8] or Streptococcus thermophilus TH-4 [52]. The use of opportunistic pathogens, such as Escherichia coli or Enterococcus faecalis in infants, is controversial due to the abovementioned risks related to genetic exchange of virulence factors and antibiotic resistance determinants [65,66]. In all but three cases [67,86,92], the probiotics were employed to alleviate symptoms or prevent skin allergic diseases.
The effects obtained are controversial, because in several cases [41,52,85,86,87], no significant differences were found between the probiotic- and placebo-treated groups. One of the studies that did not find any significant change was a multicenter study trial with more than 1000 infants. For the cases in which significant effects were found, in most cases, the beneficial effects were slight, and in two studies, the beneficial effects were limited to specific child subgroups [8,83].
The results found regarding probiotic usage in adults and in both mother–child pairs with the aim of treating or prevent allergic diseases can be found in (Table 2).
As shown in (Table 2), most studies employed probiotics against skin allergic diseases, but they were also used against allergic rhinitis or asthma [55,89,94,99], Japanese cedar pollinosis [58], food allergies [94], and rhinoconjunctivitis [106]. All studies employed Lactobacillus or Bifidobacterium spp. as the probiotic strains, with only one exception, where mixed Propionibacterium freudereichii ssp shermanii JS were employed [94]. Unlike in the case of infants, in the case of adults or mother-infant pairs, the administration of probiotics had positive effects, except in two cases [98,104]. In these two cases, where Lactobacillus rhamnosus GG were employed in pregnant women, no beneficial effects were found.
It is important to note that probiotics are considered safe due to their widespread use in food and dairy products, even more so than a hundred years ago [23]. Studies such as systematic reviews and meta-analyses show that the use of probiotics is safe in preterm infants [108]. However, several risks can be associated with probiotic therapy in the clinical field and in vulnerable target groups, such as pregnant women, infants, and immunodeficient subjects [23]. Medical studies have shown that, although uncommon, the use of probiotics may have some side effects, such as the spread of inappropriate resistance genes in intestinal microbial populations, virulence factors in probiotic microbial strains, translocation to tissues and blood, an inflammatory response, and infections [27,109]. Commercial probiotics have also been found to contain live microorganisms not listed on their labels, which can be dangerous to an individual [110,111]. In fact, a premature infant has been reported to have died from fulminant gastrointestinal mucormycotic due to fungal contamination of a probiotic supplement used. Therefore, it is also important to use probiotics with some caution [110,111].
In addition, it should be noted that some of the studies collected have not clearly shown the effects of probiotics in treating allergies [52,84,87,97]. The studies that did not find beneficial effects on humans included those that applied Lactobacillus [82,95], mixes with Bifidobacterium [87], or Streptococcus [52] to preterm infants [52], children [52,84], and pregnant women [97]. The only link between these studies is that in all cases, probiotics were used for the treatment or prevention of atopic dermatitis, so it seems that in this pathology, the use of probiotics seems only minorly effective for this purpose.
Probiotics can be taken as pharmaceutical preparations or as functional foods, generating wider acceptance among consumers, mainly as fermented foods [49]. As the intake of functional foods shows a better consumer acceptance than pharmacological presentations, there is potential for foods that are consumed regularly when they are converted to functional foods [49]. It is true that interest is increasingly focused on the potential applications of food-derived products that can be used as tools to prevent or delay the onset of a health problem, in this case allergies. This has given rise to nutraceuticals, which are defined as “the phytocomplex if derived from a food of plant origin, and as the pool of secondary metabolites if derived from a food of animal origin, concentrated and administered in the most appropriate pharmaceutical form”. This does not stop here, but nanotechnology has enabled progress to be made towards nanonutraceuticals, which have advantages due to their remarkable properties and versatility. Alternatively, nanonization strategies for probiotics and the usefulness of nanoprobiotics in releasing encapsulated bacteria and enhancing their absorption in the gastrointestinal tract are being explored, which may be of great interest in the treatment of allergies [112].
There are also studies showing that the intake of fermented foods, such as fermented yeast, galactooligosaccharides, or fructooligosaccharides, can improve the symptoms of some allergies, such as asthma or eczema, by reducing oxidative stress and inflammation [113,114,115]. This suggests that the combined administration of probiotics and prebiotics could be useful for alleviating the symptoms of allergic patients.

4. Limitations, Conclusions, and Future Trends

Some of the studies have limitations, e.g., the reduced sample size, the randomization process, and the small number of bacterial groups used. In some cases, the probiotic dosage employed is below the minimum consensus (109 UFC/day) for the appropriate use of probiotics. Thus, the results obtained in the studies that did not reach the minimum consensus limit of the appropriate use of probiotics are of doubtful validity.
“Probiotic” means “for life”, and probiotics are defined as “live microorganisms that, when being administered in appropriate doses, confer a benefit to the health of the host”, and although the use of most probiotics is generally safe, the use of some bacterial opportunistic pathogens, such as Enterococcus or Escherichia, is controversial and should be avoided, especially in vulnerable collectives, because they can interact with endogenous commensal pathogens with bi-directional genetic exchange. Previous studies have shown that, although uncommon, the use of probiotics may have some side effects.
This review has collected different published studies that show the beneficial effects of using probiotics to treat allergic diseases. No clear beneficial effects were found in children, because in several studies, no significant differences were found between probiotic- and placebo-treated groups. Even considering that probiotics do not cure allergies, their administration can reduce the morbidity and the duration of allergy symptoms. An alternative to the administration of probiotics in supplement form would be to consume them in functional foods, which are foods produced not only for their nutritional characteristics, but also to fulfil a specific function, such as improving health and/or reducing the risk of disease, as these would be more acceptable to consumers than pharmacological presentations and easier to consume. Another increasingly emerging way would be in the form of nanoprobiotics.
While many studies have been conducted, more clinical trials in humans are needed to observe the true effects of probiotic consumption on allergic diseases, but this review gives an idea of the great benefits that are likely to result from the use of probiotics in the treatment of allergies and the administration of probiotics alongside other treatments, thus reducing the morbidity of people living with allergies. Additionally, the efficacy of probiotics is dependent also on factors such as the composition and activity of the subject’s intestinal microbiota and the derived metabolites and byproducts synthesized by the probiotic species. Thus, prior knowledge of the state of the subject’s intestinal microbiota prior to the use of the probiotic agent would be advisable to improve its effectiveness.

Author Contributions

Conceptualization, J.M.M. Literature data collection, A.L.-S., E.G.G., and P.R. Writing—original draft, A.L.-S. and A.L. Writing—review and editing, A.d.C.M. and A.L. Supervision: J.M.M. All authors have read and agreed to the published version of the manuscript.


The authors thank the European Regional Development Funds (FEDER), grant ED431C 2018/05, and Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (CyTED), grant PCI2018-093245, for covering the cost of publication.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Spacova, I.; Ceuppens, J.L.; Seys, S.F.; Petrova, M.I.; Lebeer, S. Probiotics against airway allergy: Host factors to consider. Dis. Models Mech. 2018, 11. [Google Scholar] [CrossRef] [Green Version]
  2. Ring, J. What Is Allergy. In Global Atlas of Allergy; Akdis, C.A., Agache, I., Eds.; European Academy of Allergy and Clinical Immunology: Zurich, Switzerland, 2014; pp. 2–3. [Google Scholar]
  3. Akdis, C.A.; Agache, I. (Eds.) Global Atlas of Allergy; European Academy of Allergy and Clinical Immunology: Zurich, Switzerland, 2014. [Google Scholar]
  4. Pawankar, R.; Canonica, G.W.; Holgate, S.T.; Lockey, R.F. WAO White Book on Allergy; World Allergy Organization: Milwaukee, WI, USA, 2011. [Google Scholar]
  5. Galdeano, C.M.; Cazorla, S.I.; Dumit, J.M.L.; Vélez, E.; Perdigón, G. Beneficial Effects of Probiotic Consumption on the Immune System. Ann. Nutr. Metab. 2019, 74, 115–124. [Google Scholar] [CrossRef]
  6. Liu, M.-Y.; Yang, Z.-Y.; Dai, W.-K.; Huang, J.-Q.; Li, Y.-H.; Zhang, J.; Qiu, C.-Z.; Wei, C.; Zhou, Q.; Sun, X.; et al. Protective Effect of Bifidobacterium infantis CGMCC313-2 on Ovalbumin-Induced Airway Asthma and β-Lactoglobulin-Induced Intestinal Food Allergy Mouse Models. World J. Gastroenterol. 2017, 23, 2149–2158. [Google Scholar] [CrossRef]
  7. Strachan, D.P. Hay Fever, Hygiene, and Household Size. BMJ 1989, 299, 1259–1260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Lau, S.; Gerhold, K.; Zimmermann, K.; Ockeloen, C.W.; Rossberg, S.; Wagner, P.; Sulser, C.; Bunikowski, R.; Witt, I.; Wauer, J.; et al. Oral Application of Bacterial Lysate in Infancy Decreases the Risk of Atopic Dermatitis in Children with 1 Atopic Parent in a Randomized, Placebo-Controlled Trial. J. Allergy Clin. Immunol. 2012, 129, 1040–1047. [Google Scholar] [CrossRef] [PubMed]
  9. Bloomfield, S.F.; Stanwell-Smith, R.; Crevel, R.W.R.; Pickup, J. Too Clean, or Not Too Clean: The Hygiene Hypothesis and Home Hygiene. Clin. Exp. Allergy 2006, 36, 402–425. [Google Scholar] [CrossRef]
  10. Del Giudice, M.M.; Leonardi, S.; Maiello, N.; Brunese, F.P. Food Allergy and Probiotics in Childhood. J. Clin. Gastroenterol. 2010, 44, S22–S25. [Google Scholar] [CrossRef] [PubMed]
  11. Leavy, O. Old McDonald Had a Farm (but No Asthma)! Nat. Rev. Immunol. 2016, 16, 535. [Google Scholar] [CrossRef]
  12. Schuijs, M.J.; Willart, M.A.; Vergote, K.; Gras, D.; Deswarte, K.; Ege, M.J.; Madeira, F.B.; Beyaert, R.; Van Loo, G.; Bracher, F.; et al. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 2015, 349(6252), 1106–1110. [Google Scholar] [CrossRef] [PubMed]
  13. Ojwang, V.; Nwaru, B.I.; Takkinen, H.M.; Kaila, M.; Niemelä, O.; Haapala, A.M.; Ilonen, J.; Toppari, J.; Hyöty, H.; Knip, M.; et al. Early exposure to cats, dogs and farm animals and the risk of childhood asthma and allergy. Pediatr. Allergy Immunol. 2020, 31(3), 265–272. [Google Scholar] [CrossRef] [PubMed]
  14. Brick, T.; Hettinga, K.; Kirchner, B.; Pfaffl, M.W.; Ege, M.J. The beneficial effect of farm milk consumption on asthma, allergies, and infections: From meta-analysis of evidence to clinical trial. J. Allergy Clin. Immunol. Pract. 2020, 8(3), 878–889.e3. [Google Scholar] [CrossRef] [PubMed]
  15. Yu, J.E.; Miller, R.L. Got Milk? Understanding the Farm Milk Effect in Allergy and Asthma Prevention. J. Allergy Clin. Immunol. 2016, 137, 1707–1708. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Lunjani, N.; Satitsuksanoa, P.; Lukasik, Z.; Sokolowska, M.; Eiwegger, T.; O’Mahony, L. Recent Developments and Highlights in Mechanisms of Allergic Diseases: Microbiome. Allergy 2018, 73, 2314–2327. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Cionci, N.B.; Baffoni, L.; Gaggìa, F.; Di Gioia, D. Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases. Nutrients 2018, 10, 1723. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Aitoro, R.; Paparo, L.; Amoroso, A.; Di Costanzo, M.; Cosenza, L.; Granata, V.; Di Scala, C.; Nocerino, R.; Trinchese, G.; Montella, M.; et al. Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy. Nutrients 2017, 9, 672. [Google Scholar] [CrossRef] [Green Version]
  19. Chernikova, D.; Yuan, I.; Shaker, M. Prevention of Allergy with Diverse and Healthy Microbiota. Curr. Opin. Pediatr. 2019, 31, 418–425. [Google Scholar] [CrossRef] [PubMed]
  20. Rachid, R.; Chatila, T.A. The Role of the Gut Microbiota in Food Allergy. Curr. Opin. Pediatr. 2016, 28, 748–753. [Google Scholar] [CrossRef] [PubMed]
  21. Patil, S.V.; Mohite, B.V.; Patil, V.S. Probiotics for Allergic Airway Infection and Inflammations. In Probiotic Research in Therapeutics; Metzler, J.B., Ed.; Springer: Berlin/Heidelberg, Germany, 2021; pp. 295–313. [Google Scholar]
  22. Wang, X.; Yang, Y.; Huycke, M.M. Risks Associated with Enterococci as Probiotics. Food Res. Int. 2020, 129, 108788. [Google Scholar] [CrossRef]
  23. Eslami, M.; Bahar, A.; Keikha, M.; Karbalaei, M.; Kobyliak, N.; Yousefi, B. Probiotics Function and Modulation of the Immune System in Allergic Diseases. Allergol. Immunopathol. 2020, 48, 771–788. [Google Scholar] [CrossRef]
  24. Pawankar, R.; Canonica, G.W.; Holgate, S.T.; Lockey, R.F. Allergic Diseases and Asthma. Curr. Opin. Allergy Clin. Immunol. 2012, 12, 39–41. [Google Scholar] [CrossRef]
  25. Raftis, E.J.; Delday, M.I.; Cowie, P.; McCluskey, S.M.; Singh, M.D.; Ettorre, A.; Mulder, I.E. Bifidobacterium Breve MRx0004 Protects against Airway Inflammation in a Severe Asthma Model by Suppressing Both Neutrophil and Eosinophil Lung Infiltration. Sci. Rep. 2018, 8, 1–13. [Google Scholar] [CrossRef]
  26. Raposo, A.; Pérez, E.; Tinoco de Faria, C.; Carrascosa, C. Allergen Management as a Key Issue in Food Safety. In Food Safety and Protection; Ravishankar Rai, V., Bai, J.A., Eds.; CRC Press: Boca Ratón, FL, USA, 2017; pp. 195–242. [Google Scholar]
  27. Rad, A.H.; Maleki, L.A.; Kafil, H.S.; Abbasi, A. Postbiotics: A Novel Strategy in Food Allergy Treatment. Crit. Rev. Food Sci. Nutr. 2021, 61, 492–499. [Google Scholar] [CrossRef]
  28. Prince, B.T.; Mandel, M.J.; Nadeau, K.; Singh, A.M. Gut Microbiome and the Development of Food Allergy and Allergic Disease. Pediatr. Clin. North Am. 2015, 62, 1479–1492. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  29. Choi, I.S. Gender-Specific Asthma Treatment. Allergy Asthma Immunol. Res. 2011, 3, 74–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  30. Leynaert, B.; Sunyer, J.; Garcia-Esteban, R.; Svanes, C.; Jarvis, D.; Cerveri, I.; Dratva, J.; Gislason, T.; Heinrich, J.; Janson, C.; et al. Gender Differences in Prevalence, Diagnosis and Incidence of Allergic and Non-allergic Asthma: A Population-Based Cohort. Thorax 2012, 67, 625–631. [Google Scholar] [CrossRef] [Green Version]
  31. Triebner, K.; Johannessen, A.; Puggini, L.; Benediktsdóttir, B.; Bertelsen, R.J.; Bifulco, E.; Dharmage, S.C.; Dratva, J.; Franklin, K.A.; Gíslason, T.; et al. Menopause as a Predictor of New-Onset Asthma: A Longitudinal Northern European Population Study. J. Allergy Clin. Immunol. 2016, 137, 50–57. [Google Scholar] [CrossRef]
  32. Mendes, E.; Acetturi, B.G.; Thomas, A.M.; Martins, F.D.S.; Crisma, A.R.; Murata, G.; Braga, T.T.; Camâra, N.O.S.; Franco, A.L.D.S.; Setubal, J.C.; et al. Prophylactic Supplementation of Bifidobacterium longum 51A Protects Mice from Ovariectomy-Induced Exacerbated Allergic Airway Inflammation and Airway Hyperresponsiveness. Front. Microbiol. 2017, 8, 1732. [Google Scholar] [CrossRef]
  33. Greiner, A.N.; Hellings, P.W.; Rotiroti, G.; Scadding, G.K. Allergic Rhinitis. Lancet 2011, 378, 2112–2122. [Google Scholar] [CrossRef]
  34. Bousquet, J.; van Cauwenberge, P.; Khaltaev, N. Allergic Rhinitis and Its Impact on Asthma. J. Allergy Clin. Immunol. 2001, 108, S147–S334. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Bjermer, L. Time for a Paradigm Shift in Asthma Treatment: From Relieving Bronchospasm to Controlling Systemic Inflammation. J. Allergy Clin. Immunol. 2007, 120, 1269–1275. [Google Scholar] [CrossRef] [PubMed]
  36. Lai, C.K.W.; Beasley, R.; Crane, J.; Foliaki, S.; Shah, J.; Weiland, S.; the ISAAC Phase Three Study Group. Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2009, 64, 476–483. [Google Scholar] [CrossRef] [Green Version]
  37. Church, M.K.; Weller, K.; Stock, P.; Maurer, M. Chronic spontaneous urticaria in children: Itching for insight. Pediatr. Allergy Immunol. 2011, 22, 1–8. [Google Scholar] [CrossRef]
  38. Zuberbier, T.; Asero, R.; Bindslev-Jensen, C.; Canonica, G.W.; Church, M.K.; Giménez-Arnau, A.; Grattan, C.E.H.; Kapp, A.; Merk, H.F.; Rogala, B.; et al. EAACI/GA2LEN/EDF/WAO Guideline: Definition, Classification and Diagnosis of Urticaria. Allergy 2009, 64, 1417–1426. [Google Scholar] [CrossRef]
  39. Avena-Woods, C. Overview of Atopic Dermatitis. Am. J. Manag. Care 2017, 23, S115–S123. [Google Scholar] [PubMed]
  40. Langan, S.M.; Irvine, A.D.; Weidinger, S. Atopic Dermatitis. Lancet 2020, 396, 345–360. [Google Scholar] [CrossRef]
  41. Yang, H.-J.; Min, T.K.; Lee, H.W.; Pyun, B.Y. Efficacy of Probiotic Therapy on Atopic Dermatitis in Children: A Randomized, Double-blind, Placebo-controlled Trial. Allergy Asthma Immunol. Res. 2014, 6, 208–215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Mortz, C.G.; Andersen, K.E. New Aspects in Allergic Contact Dermatitis. Curr. Opin. Allergy Clin. Immunol. 2008, 8, 428–432. [Google Scholar] [CrossRef]
  43. Nwaru, I.B.; Hickstein, L.; Panesar, S.S.; Muraro, A.; Werfel, T.; Cardona, V.; Dubois, A.E.J.; Halken, S.; Hoffmannsommergruber, K.; Poulsen, L.K.; et al. The Epidemiology of Food Allergy in Europe: A Systematic Review and Meta-Analysis. Allergy 2014, 69, 62–75. [Google Scholar] [CrossRef] [Green Version]
  44. Panesar, S.S.; Javad, S.; De Silva, D.; Nwaru, B.I.; Hickstein, L.; Muraro, A.; Roberts, G.; Worm, M.; Bilò, M.B.; Cardona, V.; et al. The Epidemiology of Anaphylaxis in Europe: A Systematic Review. Allergy 2013, 68, 1353–1361. [Google Scholar] [CrossRef] [PubMed]
  45. Lopez-Santamarina, A.; Miranda, J.M.; Mondragon, A.D.C.; Lamas, A.; Cardelle-Cobas, A.; Franco, C.M.; Cepeda, A. Potential Use of Marine Seaweeds as Prebiotics: A Review. Molecules 2020, 25, 1004. [Google Scholar] [CrossRef] [Green Version]
  46. Lynch, S.V.; Pedersen, O. The Human Intestinal Microbiome in Health and Disease. N. Engl. J. Med. 2016, 375, 2369–2379. [Google Scholar] [CrossRef] [Green Version]
  47. FAO/WHO Food and Agriculture Organization of the United Nations/World Health Organization. Guidelines for the Evaluation of Probiotics in Food. Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food; FAO/WHO Food and Agriculture Organization of the United Nations/World Health Organization: Rome, Italy, 2002. [Google Scholar]
  48. Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Scope and Appropriate Use of the Term Probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514. [Google Scholar] [CrossRef] [Green Version]
  49. Lopez-Santamarina, A.; Lamas, A.; Mondragón, A.D.C.; Cardelle-Cobas, A.; Regal, P.; Rodriguez-Avila, J.A.; Miranda, J.M.; Franco, C.M.; Cepeda, A. Probiotic Effects against Virus Infections: New Weapons for an Old War. Foods 2021, 10, 130. [Google Scholar] [CrossRef] [PubMed]
  50. Anatriello, E.; Cunha, M.; Nogueira, J.; Carvalho, J.L.; Sá, A.K.; Miranda, M.; Castro-Faria-Neto, H.; Keller, A.C.; Aimbire, F. Oral Feeding of Lactobacillus Bulgaricus N45.10 Inhibits the Lung Inflammation and Airway Remodeling in Murine Allergic Asthma: Relevance to the Th1/Th2 Cytokines and STAT6/T-bet. Cell. Immunol. 2019, 341. [Google Scholar] [CrossRef]
  51. Ezendam, J.; De Klerk, A.; Gremmer, E.R.; Van Loveren, H. Effects of Bifidobacterium Animalis Administered during Lactation on Allergic and Autoimmune Responses in Rodents. Clin. Exp. Immunol. 2008, 154, 424–431. [Google Scholar] [CrossRef]
  52. Plummer, E.L.; Lozinsky, A.C.; Tobin, J.M.; Uebergang, J.B.; Axelrad, C.; Garland, S.M.; Jacobs, S.E.; Tang, M.L.K.; the ProPrems Study Group. Postnatal Probiotics and Allergic Disease in Very Preterm Infants: Sub-Study to the Proprems Randomized Trial. Allergy 2020, 75, 127–136. [Google Scholar] [CrossRef] [PubMed]
  53. Torow, N.; Hornef, M.W. The Neonatal Window of Opportunity: Setting the Stage for Life-Long Host-Microbial Interaction and Immune Homeostasis. J. Immunol. 2017, 198, 557–563. [Google Scholar] [CrossRef]
  54. Canani, R.B.; Nocerino, R.; Terrin, G.; Frediani, T.; Lucarelli, S.; Cosenza, L.; Passariello, A.; Leone, L.; Granata, V.; Di Costanzo, M.; et al. Formula Selection for Management of Children with Cow’s Milk Allergy Influences the Rate of Acquisition of Tolerance: A Prospective Multicenter Study. J. Pediatr. 2013, 163, 771–777.e1. [Google Scholar] [CrossRef] [PubMed]
  55. Kalliomäki, M. The Role of Microbiota in Allergy. Ann Nestlé 2009, 67, 19–26, (English ed.). [Google Scholar] [CrossRef]
  56. Abrahamsson, T.R.; Jakobsson, H.E.; Andersson, A.F.; Björkstén, B.; Engstrand, L.; Jenmalm, M.C. Low Diversity of the Gut Microbiota in Infants with Atopic Eczema. J. Allergy Clin. Immunol. 2012, 129, 434–440.e2. [Google Scholar] [CrossRef] [Green Version]
  57. Ismail, I.H.; Oppedisano, F.; Joseph, S.J.; Boyle, R.J.; Licciardi, P.V.; Robins-Browne, R.M.; Tang, M.L. Reduced Gut Microbial Diversity in Early Life Is Associated with Later Development of Eczema but Not Atopy in High-Risk Infants. Pediatr. Allergy Immunol. 2012, 23, 674–681. [Google Scholar] [CrossRef] [PubMed]
  58. Xiao, J.-Z.; Kondo, S.; Yanagisawa, N.; Takahashi, N.; Odamaki, T.; Iwabuchi, N.; Miyaji, K.; Iwatsuki, K.; Togashi, H.; Enomoto, K. Probiotics in the Treatment of Japanese Cedar Pollinosis: A Double-Blind Placebo-Controlled Trial. Clin. Exp. Allergy 2006, 36, 1425–1435. [Google Scholar] [CrossRef]
  59. Van Der Aa, L.B.; Van Aalderen, W.M.C.; Heymans, H.S.A.; Smitt, J.H.S.; Nauta, A.J.; Knippels, L.M.J.; Ben Amor, K.; Sprikkelman, A.B. The Synbad Study Group Synbiotics Prevent Asthma-like Symptoms in Infants with Atopic Dermatitis. Allergy 2011, 66, 170–177. [Google Scholar] [CrossRef] [PubMed]
  60. Forsberg, A.; West, C.E.; Prescott, S.L.; Jenmalm, M.C. Pre-And Probiotics for Allergy Prevention: Time to Revisit Recommendations? Clin. Exp. Allergy 2016, 46, 1506–1521. [Google Scholar] [CrossRef] [PubMed]
  61. Hou, Q.; Zhao, F.; Liu, W.; Lv, R.; Khine, W.W.T.; Han, J.; Sun, Z.; Lee, Y.-K.; Zhang, H. Probiotic-Directed Modulation of Gut Microbiota Is Basal Microbiome Dependent. Gut Microbes 2020, 12, 1–20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Ma, C.; Huo, D.; You, Z.; Peng, Q.; Jiang, S.; Chang, H.; Zhang, J.; Zhang, H. Differential Pattern of Indigenous Microbiome Responses to Probiotic Bifidobacterium Lactis V9 Consumption across Subjects. Food Res. Int. 2020, 136, 109496. [Google Scholar] [CrossRef] [PubMed]
  63. Rodriguez, J.; Hiel, S.; Neyrinck, A.M.; Le Roy, T.; Pötgens, S.A.; Leyrolle, Q.; Pachikian, B.D.; Gianfrancesco, M.A.; Cani, P.D.; Paquot, N.; et al. Discovery of the Gut Microbial Signature Driving the Efficacy of Prebiotic Intervention in Obese Patients. Gut 2020, 69, 1975–1987. [Google Scholar] [CrossRef]
  64. Zmora, N.; Zilberman-Schapira, G.; Suez, J.; Mor, U.; Dori-Bachash, M.; Bashiardes, S.; Kotler, E.; Zur, M.; Regev-Lehavi, D.; Brik, R.B.-Z.; et al. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell 2018, 174, 1388–1405.e21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Doron, S.; Snydman, D.R. Risk and Safety of Probiotics. Clin. Infect. Dis. 2015, 60, S129–S134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Wang, W.; Luo, X.; Zhang, Q.; He, X.; Zhang, Z.; Wang, X. Bifidobacterium infantis Relieves Allergic Asthma in Mice by Regulating Th1/Th2. Med. Sci. Monit. 2020, 26, e920583-1. [Google Scholar] [CrossRef]
  67. Del Giudice, M.M.; Indolfi, C.; Capasso, M.; Maiello, N.; Decimo, F.; Ciprandi, G. Bifidobacterium Mixture (B longum BB536, B Infantis M-63, B breve M-16V) Treatment in Children with Seasonal Allergic Rhinitis and Intermittent Asthma. Ital. J. Pediatr. 2017, 43, 25. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  68. Taniuchi, S.; Hattori, K.; Yamamoto, A.; Sasai, M.; Hatano, Y.; Kojima, T.; Kobayashi, Y.; Iwamoto, H.; Yaeshima, T. Admin-istration of Bifidobacterium to Infants with Atopic Dermatitis: Changes in Fecal Microflora and Clinical Symptoms. J. Appl. Res. 2005, 5, 387–396. [Google Scholar]
  69. Enomoto, T.; Sowa, M.; Nishimori, K.; Shimazu, S.; Yoshida, A.; Yamada, K.; Furukawa, F.; Nakagawa, T.; Yanagisawa, N.; Iwabuchi, N.; et al. Effects of Bifidobacterial Supplementation to Pregnant Women and Infants in the Prevention of Allergy Development in Infants and on Fecal Microbiota. Allergol. Int. 2014, 63, 575–585. [Google Scholar] [CrossRef] [Green Version]
  70. Cuello-Garcia, C.A.; Brożek, J.L.; Fiocchi, A.; Pawankar, R.; Yepes-Nuñez, J.J.; Terracciano, L.; Gandhi, S.; Agarwal, A.; Zhang, Y.; Schünemann, H.J. Probiotics for the Prevention of Allergy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Allergy Clin. Immunol. 2015, 136, 952–961. [Google Scholar] [CrossRef] [PubMed]
  71. Zhang, G.-Q.; Hu, H.-J.; Liu, C.-Y.; Zhang, Q.; Shakya, S.; Li, Z.-Y. Probiotics for Prevention of Atopy and Food Hypersensitivity in Early Childhood. Medicine 2016, 95, e2562. [Google Scholar] [CrossRef]
  72. Tang, M.L.; Lahtinen, S.J.; Boyle, R.J. Probiotics and Prebiotics: Clinical Effects in Allergic Disease. Curr. Opin. Pediatr. 2010, 22, 626–634. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Zhang, B.; An, J.; Shimada, T.; Liu, S.; Maeyama, K. Oral Administration of Enterococcus Faecalis FK-23 Suppresses Th17 Cell Development and Attenuates Allergic Airway Responses in Mice. Int. J. Mol. Med. 2012, 30, 248–254. [Google Scholar] [CrossRef] [PubMed]
  74. Won, T.J.; Kim, B.; Lee, Y.; Bang, J.S.; Oh, E.S.; Yoo, J.-S.; Hyung, K.E.; Yoon, J.; Hwang, S.; Park, E.S.; et al. Therapeutic Potential of Lactobacillus Plantarum CJLP133 for House-Dust Mite-Induced Dermatitis in NC/Nga Mice. Cell. Immunol. 2012, 277, 49–57. [Google Scholar] [CrossRef]
  75. Choi, C.-Y.; Kim, Y.-H.; Oh, S.; Lee, H.; Kim, J.; Park, S.; Kim, H.; Lee, S.; Chun, T. Anti-inflammatory Potential of a Heat-Killed Lactobacillus Strain Isolated from Kimchi on House Dust Mite-Induced Atopic Dermatitis in NC/Nga Mice. J. Appl. Microbiol. 2017, 123, 535–543. [Google Scholar] [CrossRef]
  76. Kim, J.Y.; Kwon, J.H.; Ahn, S.H.; Lee, S.I.; Han, Y.S.; Choi, Y.O.; Lee, S.Y.; Ahn, K.M.; Ji, G.E. Effect of Probiotic MIX (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the Primary Prevention of Eczema: A Double-Blind, Randomized, Placebo-Controlled Trial. Pediatr. Allergy Immunol. 2010, 21, e386–e393. [Google Scholar] [CrossRef] [PubMed]
  77. Viljanen, M.; Savilahti, E.; Haahtela, T.; Juntunen-Backman, K.; Korpela, R.; Poussa, T.; Tuure, T.; Kuitunen, M. Probiotics in the Treatment of Atopic Eczema/Dermatitis Syndrome in Infants: A Double-Blind Placebo-Controlled Trial. Allergy 2005, 60, 494–500. [Google Scholar] [CrossRef]
  78. Simpson, M.R.; Dotterud, C.K.; Storrø, O.; Johnsen, R.; Øien, T. Perinatal Probiotic Supplementation in the Prevention of Allergy Related Disease: 6 Year Follow up of a Randomised Controlled Trial. BMC Dermatol. 2015, 15, 1–8. [Google Scholar] [CrossRef] [Green Version]
  79. Loo, E.X.; Llanora, G.V.; Lu, Q.; Aw, M.M.; Lee, B.W.; Shek, L.P. Supplementation with Probiotics in the First 6 Months of Life Did Not Protect against Eczema and Allergy in At-Risk Asian Infants: A 5-Year Follow-Up. Int. Arch. Allergy Immunol. 2014, 163, 25–28. [Google Scholar] [CrossRef]
  80. Isolauri, E.; Arvola, T.; Sütas, Y.; Moilanen, E.; Salminen, S. Probiotics in the Management of Atopic Eczema. Clin. Exp. Allergy 2000, 30, 1605–1610. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  81. Rosenfeldt, V.; Benfeldt, E.; Nielsen, S.D.; Michaelsen, K.F.; Jeppesen, D.L.; Valerius, N.H.; Paerregaard, A. Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J. Allergy Clin. Immunol. 2003, 111, 389–395. [Google Scholar] [CrossRef] [PubMed]
  82. Weston, S.; Halbert, A.; Richmond, P.; Prescott, S.L. Effects of Probiotics on Atopic Dermatitis: A Randomised Controlled Trial. Arch. Dis. Child. 2005, 90, 892–897. [Google Scholar] [CrossRef] [PubMed]
  83. Sistek, D.; Kelly, R.; Wickens, K.; Stanley, T.; Fitzharris, P.; Crane, J. Is the Effect of Probiotics on Atopic Dermatitis Confined to Food Sensitized Children? Clin. Exp. Allergy 2006, 36, 629–633. [Google Scholar] [CrossRef]
  84. Brouwer, M.L.; Wolt-Plompen, S.A.A.; Dubois, A.E.J.; Van Der Heide, S.; Jansen, D.F.; Hoijer, M.A.; Kauffman, H.F.; Duiverman, E.J. No Effects of Probiotics on Atopic Dermatitis in Infancy: A Randomized Placebo-Controlled Trial. Clin. Exp. Allergy 2006, 36, 899–906. [Google Scholar] [CrossRef] [PubMed]
  85. Taylor, A.L.; Dunstan, J.A.; Prescott, S.L. Probiotic Supplementation for the First 6 Months of Life Fails to Reduce the Risk of Atopic Dermatitis and Increases the Risk of Al-Lergen Sensitization in High-Risk Children: A Randomized Controlled Trial. J. Allergy Clin. Immunol. 2007, 119, 184–191. [Google Scholar] [CrossRef] [PubMed]
  86. Hol, J.; Van Leer, E.H.; Schuurman, B.E.E.; De Ruiter, L.F.; Samsom, J.N.; Hop, W.; Neijens, H.J.; De Jongste, J.C.; Nieuwenhuis, E.E. The Acquisition of Tolerance toward Cow’s Milk through Probiotic Supplementation: A Randomized, Controlled Trial. J. Allergy Clin. Immunol. 2008, 121, 1448–1454. [Google Scholar] [CrossRef] [PubMed]
  87. Soh, S.E.; Aw, M.; Gerez, I.; Chong, Y.S.; Rauff, M.; Ng, Y.P.M.; Wong, H.B.; Pai, N.; Lee, B.W.; Shek, L.P.-C. Probiotic Supplementation in the First 6 Months of Life in at Risk Asian Infants—Effects on Eczema and Atopic Sensitization at the Age of 1 Year. Clin. Exp. Allergy 2009, 39, 571–578. [Google Scholar] [CrossRef] [PubMed]
  88. West, C.E.; Hammarström, M.-L.; Hernell, O. Probiotics during Weaning Reduce the Incidence of Eczema. Pediatr. Allergy Immunol. 2009, 20, 430–437. [Google Scholar] [CrossRef] [PubMed]
  89. Dotterud, C.K.; Storrø, O.; Johnsen, R.; Øien, T. Probiotics in Pregnant Women to Prevent Allergic Disease: A Randomized, Double-Blind Trial. Br. J. Dermatol. 2010, 163, 616–623. [Google Scholar] [CrossRef]
  90. Nermes, M.; Kantele, J.M.; Atosuo, T.J.; Salminen, S.; Isolauri, E. Interaction of Orally Administered Lactobacillus Rhamnosus GG with Skin and Gut Microbiota and Humoral Immunity in Infants with Atopic Dermatitis. Clin. Exp. Allergy 2010, 41, 370–377. [Google Scholar] [CrossRef] [PubMed]
  91. Wang, I.-J.; Wang, J. Children with Atopic Dermatitis Show Clinical Improvement Afterlactobacillus exposure. Clin. Exp. Allergy 2015, 45, 779–787. [Google Scholar] [CrossRef]
  92. Cabana, M.D.; Mckean, M.; Caughey, A.B.; Fong, L.; Lynch, S.; Wong, A.; Leong, R.; Boushey, H.A.; Hilton, J.F. Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial. Pediatrics 2017, 140, e20163000. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  93. Navarro-López, V.; Ramírez-Boscá, A.; Ramón-Vidal, D.; Ruzafa-Costas, B.; Genovés-Martínez, S.; Chenoll-Cuadros, E.; Carrión-Gutiérrez, M.; De La Parte, J.H.; Prieto-Merino, D.; Codoñer-Cortés, F.M. Effect of Oral Administration of a Mixture of Probiotic Strains on SCORAD Index and Use of Topical Steroids in Young Patients with Moderate Atopic Dermatitis. JAMA Dermatol. 2018, 154, 37–43. [Google Scholar] [CrossRef] [PubMed]
  94. Kukkonen, K.; Savilahti, E.; Haahtela, T.; Juntunen-Backman, K.; Korpela, R.; Poussa, T.; Tuure, T.; Kuitunen, M. Probiotics and Prebiotic Galacto-Oligosaccharides in the Prevention of Allergic Diseases: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Allergy Clin. Immunol. 2007, 119, 192–198. [Google Scholar] [CrossRef]
  95. Huurre, A.; Laitinen, K.; Rautava, S.; Korkeamäki, M.; Isolauri, E. Impact of Maternal Atopy and Probiotic Supplementation during Pregnancy on Infant Sensitization: A Double-Blind Placebo-Controlled Study. Clin. Exp. Allergy 2008, 38, 1342–1348. [Google Scholar] [CrossRef]
  96. Wickens, K.; Black, P.N.; Stanley, T.V.; Mitchell, E.; Fitzharris, P.; Tannock, G.W.; Purdie, G.; Crane, J. A Differential Effect of 2 Probiotics in the Prevention of Eczema and Atopy: A Double-Blind, Randomized, Placebo-Controlled Trial. J. Allergy Clin. Immunol. 2008, 122, 788–794. [Google Scholar] [CrossRef]
  97. Kopp, M.V.; Hennemuth, I.; Heinzmann, A.; Urbanek, R. Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation. Pediatrics 2008, 121, e850–e856. [Google Scholar] [CrossRef]
  98. Niers, L.; Martin, R.; Rijkers, G.; Sengers, F.; Timmerman, H.; Van Uden, N.; Smidt, H.; Kimpen, J.; Hoekstra, M. The Effects of Selected Probiotic Strains on the Development of Eczema (The PandA Study). Allergy 2009, 64, 1349–1358. [Google Scholar] [CrossRef] [PubMed]
  99. Koyama, T.; Kirjavainen, P.V.; Fisher, C.; Anukam, K.; Summers, K.; Hekmat, S.; Reid, G. Development and Pilot Evaluation of a Novel Probiotic Mixture for the Management of Seasonal Allergic Rhinitis. Can. J. Microbiol. 2010, 56, 730–738. [Google Scholar] [CrossRef] [PubMed]
  100. Boyle, R.J.; Ismail, I.H.; Kivivuori, S.; Licciardi, P.V.; Robins-Browne, R.M.; Mah, L.-J.; Axelrad, C.; Moore, S.; Donath, S.; Carlin, J.B.; et al. Lactobacillus GG Treatment during Pregnancy for the Prevention of Eczema: A Randomized Controlled Trial. Allergy 2010, 66, 509–516. [Google Scholar] [CrossRef]
  101. Han, Y.; Kim, B.; Ban, J.; Lee, J.; Kim, B.J.; Choi, B.S.; Hwang, S.; Ahn, K.; Kim, J. A Randomized Trial Oflactobacillus plantarum CJLP133 for the Treatment of Atopic Dermatitis. Pediatr. Allergy Immunol. 2012, 23, 667–673. [Google Scholar] [CrossRef]
  102. Rautava, S.; Kainonen, E.; Salminen, S.; Isolauri, E. Maternal Probiotic Supplementation during Pregnancy and Breast-Feeding Reduces the Risk of Eczema in the Infant. J. Allergy Clin. Immunol. 2012, 130, 1355–1360. [Google Scholar] [CrossRef] [PubMed]
  103. Ou, C.-Y.; Kuo, H.-C.; Wang, L.; Hsu, T.-Y.; Chuang, H.; Liu, C.-A.; Chang, J.-C.; Yu, H.-R.; Yang, K.D. Prenatal and Postnatal Probiotics Reduces Maternal but Not Childhood Allergic Diseases: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin. Exp. Allergy 2012, 42, 1386–1396. [Google Scholar] [CrossRef]
  104. Inoue, Y.; Kambara, T.; Murata, N.; Komori-Yamaguchi, J.; Matsukura, S.; Takahashi, Y.; Ikezawa, Z.; Aihara, M. Effects of Oral Administration of Lactobacillus acidophilus L-92 on the Symptoms and Serum Cytokines of Atopic Dermatitis in Japanese Adults: A Double-Blind, Randomized, Clinical Trial. Int. Arch. Allergy Immunol. 2014, 165, 247–254. [Google Scholar] [CrossRef]
  105. Rø, A.D.B.; Rø, T.B.; Storrø, O.; Johnsen, R.; Videm, V.; Øien, T.; Simpson, M.R. Reduced Th22 Cell Proportion and Prevention of Atopic Dermatitis in Infants Following Maternal Probiotic Supplementation. Clin. Exp. Allergy 2017, 47, 1014–1021. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  106. Dennis-Wall, J.C.; Culpepper, T.; Nives, C., Jr.; Rowe, C.C.; Burns, A.M.; Rusch, C.T.; Federico, A.; Ukhanova, M.; Waugh, S.; Mai, V.; et al. Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) Improve Rhinoconjunctivitis-Specific Quality of Life in Individuals with Seasonal Allergies: A Double-Blind, Placebo-Controlled, Randomized Trial. Am. J. Clin. Nutr. 2017, 105, 758–767. [Google Scholar] [CrossRef] [Green Version]
  107. Prakoeswa, C.; Herwanto, N.; Prameswari, R.; Astari, L.; Sawitri, S.; Hidayati, A.; Indramaya, D.; Kusumowidagdo, E.; Surono, I. Lactobacillus plantarum IS-10506 Supplementation Reduced SCORAD in Children with Atopic Dermatitis. Benef. Microbes 2017, 8, 833–840. [Google Scholar] [CrossRef] [PubMed]
  108. Zhu, X.-L.; Tang, X.-G.; Qu, F.; Zheng, Y.; Zhang, W.-H.; Diao, Y.-Q. Bifidobacterium May Benefit the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Systematic Review and Meta-Analysis. Int. J. Surg. 2019, 61, 17–25. [Google Scholar] [CrossRef]
  109. Bertelli, C.; Pillonel, T.; Torregrossa, A.; Prod’Hom, G.; Fischer, C.J.; Greub, G.; Giannoni, E. Bifidobacterium longum Bacteremia in Preterm Infants Receiving Probiotics. Clin. Infect. Dis. 2015, 60, 924–927. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  110. Cohen, P.A. Probiotic Safety—No Guarantees. JAMA Intern. Med. 2018, 178, 1577. [Google Scholar] [CrossRef]
  111. Vallabhaneni, S.; Walker, T.A.; Lockhart, S.R.; Ng, D.; Chiller, T.; Melchreit, R.; Brandt, M.E.; Smith, R.M. Fatal Gastrointestinal Mucormycosis in a Premature Infant Associated with a Contaminated Dietary Supplement—Connecticut, 2014. MMWR. Morb. Mortal. Wkly. Rep. 2015, 64, 155–156. [Google Scholar]
  112. Durazzo, A.; Nazhand, A.; Lucarini, M.; Atanasov, A.G.; Souto, E.B.; Novellino, E.; Capasso, R.; Santini, A. An Updated Overview on Nanonutraceuticals: Focus on Nanoprebiotics and Nanoprobiotics. Int. J. Mol. Sci. 2020, 21, 2285. [Google Scholar] [CrossRef] [Green Version]
  113. Gong, S.; Ji, X.; Su, J.; Wang, Y.; Yan, X.; Wang, G.; Xiao, B.; Dong, H.; Xiang, X.; Liu, S. Yeast Fermentate Prebiotic Ameliorates Allergic Asthma, Associating with Inhibiting Inflammation and Reducing Oxidative Stress Level through Suppressing Autophagy. Mediat. Inflamm. 2021, 2021, 1–13. [Google Scholar] [CrossRef] [PubMed]
  114. Osborn, A.D.; Sinn, J.K.H. Prebiotics in Infants for Prevention of Allergy. Cochrane Database Syst. Rev. 2013, 28, CD006474. [Google Scholar] [CrossRef]
  115. Scalabrin, D.; Harris, C.; Johnston, W.H.; Berseth, C.L. Long-Term Safety Assessment in Children Who Received Hydrolyzed Protein Formulas with Lactobacillus Rhamnosus GG: A 5-Year Follow-Up. Eur. J. Nucl. Med. Mol. Imaging 2017, 176, 217–224. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Figure 1. Factors that could explain the varied effects of probiotics uncovered by different studies.
Figure 1. Factors that could explain the varied effects of probiotics uncovered by different studies.
Foods 10 00701 g001
Table 1. Use of probiotics to treat or prevent allergic diseases in infants.
Table 1. Use of probiotics to treat or prevent allergic diseases in infants.
Type of StudyProbioticDosage and Time of ExposureAllergic DiseaseMain FindingsReference
Randomized, double-blind study with 27 infants with atopic diseaseBifidobacterium lactis Bb-12 and Lactobacillus rhamnosus GG (LGG)Oral administration of 3 × 108 CFU of LGG and 109 CFU of B. lactis for 4 weeksAtopic eczemaAfter 2 months, a significant improvement in the skin condition occurred in the probiotic group. The Scoring Atopic Dermatitis (SCORAD) and concentration of soluble CD4+ decreased in the probiotic groups[80]
Double-blind, placebo-controlled, crossover
study with 58 children
Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460A dose of 1010 CFU twice daily for 6 weeksAtopic dermatitisThe duration of eczema decreased during probiotic administration. The treatment response was more pronounced in allergic patients, and the SCORAD score decreased[81]
Randomized, double-blind, placebo-controlled study with 230 infants with suspected cow’s milk allergy (CMA)LGG, L. rhamnosus LC705, B. breve Bb99 and Propionibacterium freudenreichii ssp shermanii JS Oral administration of LGG (5 × 109 CFU) or a mixture of LGG (5 × 109 CFU), L. rhamnosus LC705 (5 × 109), B. breve Bb99 (2 × 108), and Propionibacterium freudenreichii spp. shermanii JS (2 × 109) twice daily for 4 weeks.Atopic dermatitis related to cow’s milk allergyTreatment with LGG may alleviate symptoms of atopic eczema and/or dermatitis syndrome in IgE-sensitized infants[77]
Randomized, double-blind, placebo-controlled study with 56 childrenLactobacillus fermentum VRI-033 PCC1 × 109 CFU twice daily for 8 weeksAtopic dermatitisA reduction in the SCORAD index was seen in the probiotic-treated group. At the end of the study, more children treated with this probiotic had milder atopic dermatitis[82]
Randomized, placebo-controlled study with 59 children with ADL. rhamnosus and B.
A dose of 2 × 1010 CFU daily for 12 weeksAtopic dermatitisA combination of L. rhamnosus and B. lactis improved atopic dermatitis only in food-sensitized children[83]
Randomized, double-blind, placebo-controlled study with 50 infants L. rhamnosus Lrh and LGGAdministering 1, 5, 25 and 125 mL of cow’s milk formula at 30 min intervals (5 × 109 CFU/mL formula)Atopic dermatitis related to cow’s milk allergyNo clear effects were seen on the SCORAD, sensitization, inflammatory parameters, or cytokine production[84]
Randomized trial with newborns of 231 women with allergiesLactobacillus acidophilus LAVRI-A13 × 109 CFU/day for the first 6 months of lifeAtopic dermatitisAtopic dermatitis rates were similar in the probiotic and placebo groups. At 12 months, the rate of sensitization was significantly higher in the probiotic group[85]
Randomized, double-blind, placebo-controlled study with 193 infants diagnosed with cow’s milk allergy (CMA)Lactobacillus casei CRL431 and Bifidobacterium lactis BB-12107 CFU/g for each of the probiotic bacteria for 6 monthsCow’s milk allergy (CMA)Supplementation with Lactobacillus and Bifidobacterium in an extensively hydrolyzed formula did not accelerate cow’s milk tolerance in infants with CMA[86]
Double-blind, placebo-controlled, randomized trial with 253 infantsB. longum BL999 and L. rhamnosus LPROral supplementation with 1 × 107 CFU/g/day of B. longum and 2 × 107 CFU/g/day of L. rhamnosus for the first 6 monthsAtopy and eczemaNo significant effect on the prevention of eczema or allergen sensitization in the first year of life[87]
Double-blind, placebo-controlled, randomized trial with 179 infantsLactobacillus F191 × 108 CFU/day for 4–6 monthsEczemaThe cumulative incidence of eczema at 13 months was lower in the probiotic group. At 13 months, the INF-y/IL-4 ratio was higher in the probiotic group. No differences in serum concentrations of IgE[88]
Randomized, double-blind trial of children from 415 mothersLGG, B. animalis ssp. lactis
Bb-12 and L. acidophilus La-5
Milk contained 5 × 1010 CFU/day of L. rhamnosus and Bb-12. 5 × 109 CFU of L. acidophilus for 4 months, from 36 weeks of gestation to 3 months postnatallyAtopic dermatitis and asthma In the probiotic group, the cumulative incidence of atopic dermatitis was reduced but there was no effect on sensitization[89]
Randomized, double-blind study with 39 infants with ADLGGA daily intake of 3.4 × 109 CFU for 3 monthsAtopic dermatitisThe proportions of IgA- and IgM-secreting cells decreased in the probiotic group, and the proportions of CD191+ and CD27+ B cells increased[90]
Randomized, placebo-controlled trial with 606 newbornsEscherichia coli DSM 17252 and Enterococcus faecalis DSM 1644Oral bacteria lysate containing heat-killed nonpathogenic 1.5–4.5 × 107 bacteria/mL (3 × 0.7 mL/day)Atopic dermatitisA significant effect was observed in a subgroup of the probiotic group with single heredity for atopy, which was most pronounced for infants with atopic fathers[8]
Double-blind, placebo-controlled, randomized parallel study with 100 childrenMixture of L. casei, L. rhamnosus, L. plantarum, and B. lactisOral administration at 2 × 109 CFU in each strain, twice daily for 6 weeksAtopic dermatitisThe probiotic mixture did not suppress the growth of other strains, but no differences in clinical improvement were seen between the treated and placebo groups[41]
Double-blind, prospective, randomized, placebo-controlled study with 2020 childrenL. paracasei GMNL-133 and/or L. fermentum GM0902 × 109 CFU/day of L. paracasei, L. plantarum, or 4 × 109 CFU of a mixture for 3 monthsAtopic dermatitisChildren given either probiotics alone or a mixture of both showed a decrease in the severity of atopic dermatitis scores. Lower test scores were also recorded for people with skin diseases. IgE, TNF-α, and INF-y increased in the probiotic group[91]
Randomized, controlled, double-blind study with 159 newbornsLGG1010 CFU/day for the first 6 months of lifeEczema and asthmaThe estimated cumulative incidence of eczema and asthma was lower in the probiotic group at 2 years of age[92]
Prospective, double-blind, placebo-controlled, randomized study with 40 childrenB. longum BB536, Bifidobacterium infantis M-63, and B. breve M-16 VOral supplementation containing B. longum BB536 (3 × 109 CFU), B. infantis M-63 (1 × 109 CFU), and B. breve M-16 V (1 × 109 CFU) as powder in a 3 mg sachet. Administered every day for 8 weeksSeasonal allergic rhinitis and intermittent asthmaA significant improvement of symptoms and quality of life in the probiotic group[67]
Double-blind, 2-arm, placebo-controlled study with 50 children with ADB. lactis CECT 8145, B. longum CECT7347, and L. casei CECT 9104109 CFU/day of a mixture of the 3 probiotic strainsAtopic dermatitisA reduction in IL-4, IL-5, and IL-13 and a decreased activity of Th2 in the probiotic group. The SCORAD index and use of corticosteroids were also reduced in the probiotic group[93]
A multi-center, double-blind, placebo-controlled, randomized trial with 1099 very preterm infantsB. infantis BB-02, Streptococcus thermophilus TH-4, and B. lactis BB-12A combination of B. infantis BB-02 (300 × 106 CFU), S. thermophilus TH-4 (350 × 106 CFU), and B. lactis BB-12 (350 × 106). Total: 1 × 109 CFU per 1.5 g in a powder once daily, until discharged from hospital or term-corrected ageEczema, atopic sensitization, food allergy, and wheezingThere was no difference in eczema incidence between the two groups. Additionally, the incidence of atopic eczema, food allergy, wheezing, and atopic sensitization were similar in both groups[52]
Table 2. Use of probiotics to treat or prevent allergic diseases in adults and mother–infant pairs.
Table 2. Use of probiotics to treat or prevent allergic diseases in adults and mother–infant pairs.
Type of StudyProbioticDosage and Time of ExposureAllergic DiseaseMain FindingsReference
Double-blind, randomized, placebo-controlled study with 159 mothers with allergic diseases and their infantsLactobacillus rhamnosus GG (LGG)1 × 1010 CFU daily for 2–4 weeksAtopic eczema, asthma, and allergic rhinitisThe incidence of eczema in the probiotic group was halved. The concentrations of total immunoglobulin (Ig) E and positive reactions in skin-pick tests were similar in both groups[55]
Randomized, double-blind, placebo-controlled trial with 44 adultsBifidobacterium longum BB5365 × 1010 CFU twice daily for 13 weeksJapanese cedar pollinosis (JCPsis)B. longum reduced severe symptoms and medication and decreased nasal blockage in rhinorrhea, and composite scores. Improvements in all symptoms[58]
Randomized trial with newborns of 231 women with allergyLactobacillus acidophilus LAVRI-A13 × 109 CFU/day for the first 6 months of lifeAtopic dermatitisAtopic dermatitis rates were similar in the probiotic and placebo groups. At 12 months, the rate of sensitization was significantly higher in the probiotic group[85]
Double-blind, randomized, placebo-controlled study with 232 mothersL. reuteri ATCC 557301 × 108 CFU/day from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 monthsEczemaThe cumulative incidence of eczema was similar in the two groups. The probiotic group had less IgE-associated, and skin prick test reactivity was also less common[56]
Randomized, double-blind, placebo-controlled study with 2 parallel groups of 1223 pregnant womenLGG, L. rhamnosus LC705, Bifidobacterium breve Bb99, and P. freudenreichii spp. shermanii JSOral administration of LGG (5 × 109 CFU), L. rhamnosus LC705 (5 × 109), B. breve Bb99 (2 × 108), and Propionibacterium freudenreichii spp. shermanii JS (2 × 108) twice daily for 2 to 4 weeks before delivery. Their infants received the same probiotics (+ prebiotics) once daily for the first 6 monthsFood allergy, eczema, asthma, and allergic rhinitisAdministration of these probiotics significantly prevented eczema and atopic eczema[94]
Placebo-controlled, double-blind study with 171 mother–infant pairsLGG and B. lactis Bb121010 CFU/day of each probiotic from the first trimester of pregnancy to the end of exclusive breastfeedingAtopy (eczema)The concentration of TGF-b2 was higher in colostrum from dams supplemented with probiotics. This supplementation produced a protective effect against sensitization in infants at a high hereditary risk[95]
Two-center, double-blind, randomized, placebo-controlled trial with 512 pregnant women and 474 infantsL. rhamnosus HN001 and Bifidobacterium animalis spp. lactis HN019Two treatment groups: 6 × 109 CFU/d of L. rhamnosus or 9 × 109 CFU/d of B. animalis from 35 weeks of gestation until 6 months in pregnant women and from birth to 2 years in infantsEczema and atopySupplementation with only L. rhamnosus reduced the cumulative prevalence of eczema, but not atopy, by 2 years[96]
Double-blind, placebo-controlled, prospective study with 105 pregnant womenLGG5 × 109 CFU twice daily. Started 4–6 weeks before expected delivery until a postnatal period of 6 monthsAtopic dermatitisThere was no significant difference between the probiotic group and placebo groups[97]
Randomized, double-blind, placebo-controlled trial with 112 pregnant womenBifidobacterium bifidum BGN4, B. lactis AD011, and L. acidophilus AD031Mixture of probiotics (1.6 × 109 CFU/day of each probiotic) for 4–8 weeks before delivery until 6 months after deliveryEczemaThe prevalence of eczema in the probiotic-added group was lower. The cumulative incidence of eczema during the first 12 months was reduced in the probiotic group. No difference in the serum total IgE level or sensitization to food allergens[7]
Double-blind, randomized, placebo-controlled study with 156 pregnant womenB. bifidum W23 and B. lactis W521 × 109 CFU/day of each strain during the last 6 weeks of pregnancy and postnatally for 12 months to their offspringEczemaThe prevalence of eczema during the first 3 months of life was significantly lower in the probiotic group. The cumulative incidence was also lower in the probiotic group[98]
Randomized, double-blind trial of children from 415 mothersLGG, B. animalis ssp. lactis
Bb-12, and L. acidophilus La-5
Milk contained 5 × 1010 CFU/day of L. rhamnosus and Bb-12. 5 × 109 CFU of L. acidophilus for 4 months, from 36 weeks of gestation to 3 months postnatallyAtopic dermatitis and asthma In the probiotic group, the cumulative incidence of atopic dermatitis was reduced, but there was no effect on sensitization[89]
Double-blind, placebo-controlled study with 36 subjects with allergic rhinitisL. rhamnosus GR-1 and Bifidobacterium adolescentis 7007-05Added L. rhamnosus at 4% and B. adolescentis at 10% of final milk volumeRhinitisSerum IL-10 and IL-12 levels were increased in the probiotic group at the end of the grass pollen season. Additionally, the serum TFG-β levels were higher during the ragweed season[99]
Randomized controlled trial with 250 pregnant women LGG1.8 × 1010 CFU/day from 36 weeks of gestation until deliveryEczemaPrenatal probiotic treatment was only associated with decreased breast milk soluble CD14 and IgA levels[100]
Randomized, double-blind, placebo-controlled studyLactobacillus plantarum CJLP1330.5 × 1010 CFU twice a day for 12 weeksAtopic dermatitisSCORAD scores were lower with probiotic administration. Additionally, the total eosinophil counts were significantly lower, and the logarithmic IFN-c and IL-4 concentrations were decreased[101]
Parallel, double-blind, placebo-controlled study of 241 mother–infant pairsL. rhamnosus LPR, B. longum BL999, and Lactobacillus paracasei ST11Combination of L. rhamnosus and B. longum or L. paracasei and B. longum. Daily dose for each probiotic (1 × 109 CFU) for 2 months before delivery and during the first 2 months of breastfeeding. The infants were followed for 24 monthsEczemaThe risk of eczema was reduced in infants of mothers receiving combinations of probiotics during the first 24 months[102]
Prospective, double-blind, placebo-controlled study with 191 pregnant womenLGG1 × 1010 CFU/day from the second trimester of pregnancyAtopic diseasesNo significant effects of prenatal and postnatal probiotic supplementation on sensitization, development of allergic diseases, and maternal IgE levels. The allergic symptoms improved in the probiotic group[103]
Double-blind, parallel-group, placebo-controlled comparison with 49 AD patientsL. acidophilus L-9220.7 mg/day for 8 weeksAtopic dermatitisThis probiotic contributes to the suppression of Th-2-dominant inflammation and reduces atopic dermatitis symptoms in adults[104]
Randomized controlled study with 415 pregnant womenLGG, B. animalis spp. Lactis Bb-12, and L. acidophilus La-5Daily dose of LGG (5 × 1010 CFU), B. animalis spp. Lactis Bb-12 (5 × 1010 CFU), and L. acidophilus La-5 (5 × 109 CFU) from 36 weeks of gestation to 3 months postnatalAtopic dermatitisSupplementation with a combination of these probiotics reduced the proportion of Th22 cells. However, the proportion of Tregs, Th1, Th2, and Th17 cells and the Th1/Th2 ratio in the offspring were not affected[105]
Double-blind, placebo-controlled, parallel, randomized clinical study with 173 participantsLactobacillus gasseri KS-13, B. bifidum G9-1, and B. longum MM-2Each capsule (350 mg) contained L. gasseri KS-13 (1.2 billion CFU), B. bifidum G9-1 (0.15 billion), and B. longum MM-2 (0.15 billion)Rhinoconjunctivitis-specificAn improvement in the rhinoconjunctivitis-specific quality of life during allergy season was seen in the probiotic group[106]
Randomized, double-blind, placebo-controlled study with 22 AD subjectsL. plantarum IS-105061010 CFU/day for 12 weeksAtopic dermatitisReduction in clinical symptoms in AD children and decreased SCORAD and levels of serum IgE, IL-4, and IL-17. The probiotic acted through the downregulation of the Th2-adaptive immune response[107]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Lopez-Santamarina, A.; Gonzalez, E.G.; Lamas, A.; Mondragon, A.d.C.; Regal, P.; Miranda, J.M. Probiotics as a Possible Strategy for the Prevention and Treatment of Allergies. A Narrative Review. Foods 2021, 10, 701.

AMA Style

Lopez-Santamarina A, Gonzalez EG, Lamas A, Mondragon AdC, Regal P, Miranda JM. Probiotics as a Possible Strategy for the Prevention and Treatment of Allergies. A Narrative Review. Foods. 2021; 10(4):701.

Chicago/Turabian Style

Lopez-Santamarina, Aroa, Esther Gonzalez Gonzalez, Alexandre Lamas, Alicia del Carmen Mondragon, Patricia Regal, and Jose Manuel Miranda. 2021. "Probiotics as a Possible Strategy for the Prevention and Treatment of Allergies. A Narrative Review" Foods 10, no. 4: 701.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop