Allergic rhinitis affects 60 million of the U.S. population, 1.4 billion of the global population, and its prevalence appears to be increasing. The duration and severity of allergic rhinitis symptoms place a substantial burden on patient's quality of life, sleep, work productivity, and activity. The health impact of allergic rhinitis is compounded by associated complications and comorbidities including asthma, otitis media, sinusitis, and nasal polyps. Allergic rhinitis symptoms result from a complex, allergen-driven mucosal inflammatory process, modulated by immunoglobulin E (IgE), and caused by interplay between resident and infiltrating inflammatory cells and a number of vasoactive and proinflammatory mediators, including cytokines. This allergic response may be characterized as three phases: IgE sensitization, allergen challenge, and elicitation of symptoms. A thorough allergic history is the best tool for the diagnosis of allergic rhinitis, the establishment of which is achieved by correlating the patient's history and physical exam with an assessment for the presence of specific IgE antibodies to relevant aeroallergens determined by skin testing or by in vitro assay. Management of allergic rhinitis includes modifying environmental exposures, implementing pharmacotherapy, and, in select cases, administering allergen-specific immunotherapy. Intranasal therapeutic options include antihistamines, anticholinergic agents, corticosteroids (aqueous or aerosol), mast cell stabilizers, saline, and brief courses of decongestants. Selection of pharmacotherapy is based on the severity and chronicity of symptoms with the most effective medications being intranasal corticosteroids and intranasal antihistamines, which can be used in combination (separately or in fixed dose) for more difficult to control allergic rhinitis.

On allergic rhinitis

Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, including the gastrointestinal tract. While this beneficial effect was originally thought to stem from improvements in the intestinal microbial balance, there is now substantial evidence that probiotics can also provide benefits by modulating immune functions. In animal models, probiotic supplementation is able to provide protection from spontaneous and chemically induced colitis by downregulating inflammatory cytokines or inducing regulatory mechanisms in a strain-specific manner. In animal models of allergen sensitization and murine models of asthma and allergic rhinitis, orally administered probiotics can strain-dependently decrease allergen-specific IgE production, in part by modulating systemic cytokine production. Certain probiotics have been shown to decrease airway hyperresponsiveness and inflammation by inducing regulatory mechanisms. Promising results have been obtained with probiotics in the treatment of human inflammatory diseases of the intestine and in the prevention and treatment of atopic eczema in neonates and infants. However, the findings are too variable to allow firm conclusions as to the effectiveness of specific probiotics in these conditions.

/pdf/probiotics-and-immunity-16j2cffmgr.pdf

Probiotics and immunity

A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.

Rebuilding the Gut Microbiota Ecosystem.

Objectives To catalog what is known about the safety of interventions containing Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus strains used as probiotic agents in research to reduce the risk of, prevent, or treat disease. Data sources We searched 12 electronic databases, references of included studies, and pertinent reviews for studies addressing the safety of probiotics from database inception to August 2010 without language restriction. Review methods We identified intervention studies on probiotics that reported the presence or absence of adverse health outcomes in human participants, without restriction by study design, participant type, or clinical field. We investigated the quantity, quality, and nature of adverse events. Results The search identified 11,977 publications, of which 622 studies were included in the review. In 235 studies, only nonspecific safety statements were made ("well tolerated"); the remaining 387 studies reported the presence or absence of specific adverse events. Interventions and adverse events were poorly documented. A number of case studies described fungemia and some bacteremia potentially associated with administered probiotic organisms. Controlled trials did not monitor routinely for such infections and primarily reported on gastrointestinal adverse events. Based on reported adverse events, randomized controlled trials (RCTs) showed no statistically significantly increased relative risk (RR) of the overall number of experienced adverse events (RR 1.00; 95% confidence interval [CI]: 0.93, 1.07, p=0.999); gastrointestinal; infections; or other adverse events, including serious adverse events (RR 1.06; 95% CI: 0.97, 1.16; p=0.201), associated with short-term probiotic use compared to control group participants; long-term effects are largely unknown. Existing studies primarily examined Lactobacillus alone or in combination with other genera, often Bifidobacterium. Few studies directly compared the safety among different intervention or participant characteristics. Indirect comparisons indicated that effects of delivery vehicles (e.g., yogurt, dairy) should be investigated further. Case studies suggested that participants with compromised health are most likely to experience adverse events associated with probiotics. However, RCTs in medium-risk and critically ill participants did not report a statistically significantly increased risk of adverse events compared to control group participants. Conclusions There is a lack of assessment and systematic reporting of adverse events in probiotic intervention studies, and interventions are poorly documented. The available evidence in RCTs does not indicate an increased risk; however, rare adverse events are difficult to assess, and despite the substantial number of publications, the current literature is not well equipped to answer questions on the safety of probiotic interventions with confidence.

Safety of probiotics used to reduce risk and prevent or treat disease.

The emergence of egg allergy has had both industrial and clinical implications. In industrialized countries, egg allergy accounts for one of the most prevalent food hypersensitivities, especially in children. Atopic dermatitis represents the most common clinical manifestation in infancy; however, the range of clinical signs is broad and encompasses life-threatening anaphylaxis. The dominant egg allergens are proteins and are mainly present in the egg white, for example, ovalbumin, ovomucoid, ovotransferrin, and lysozyme. However, egg yolk also displays low-level allergenicity, for example, alpha-livetin. Strict avoidance of the offending food remains the most common recommendation for egg-allergic individuals. Nevertheless, the omnipresence of egg-derived components in prepackaged or prepared foods makes it difficult. Therefore, more efficient preventive approaches are investigated to protect consumers from inadvertent exposure and ensuing adverse reactions. On the one hand, commercial kits have become readily available that allow for the detection of egg contaminants at trace levels. On the other hand, attempts to produce hypoallergenic egg-containing products through food-processing techniques have met with promising results, but the approach is limited due to its potentially undesirable effects on the unique functional and sensory attributes of egg proteins. Therefore, the development of preventive or curative strategies for egg allergy remains strongly warranted. Pilot studies have suggested that oral immunotherapy (IT) with raw or cooked preparations of egg may represent a safe alternative, immediately available to allergic subjects, but remains applicable to only nonanaphylactic patients. Due to the limitations of conventional IT, novel forms of immunotherapy are sought based on information obtained from the molecular characterization of major egg allergens. In the past decade, promising approaches to the treatment and prevention of egg allergy have been explored and include, among others, the production of hypoallergenic recombinant egg proteins, the development of customized peptides, and bacterial-mediated immunotherapy. Nonspecific approaches have also been evaluated, and preliminary trials with the use of probiotic bacteria have yielded encouraging results. The current understanding of egg allergens offers novel approaches toward the making of food products safe for human consumption and the development of efficient immunotherapeutic strategies.

Recent advances in the understanding of egg allergens: basic, industrial, and clinical perspectives.

Recent studies have suggested that oral bacteriotherapy with probiotics might be useful in the management of allergic diseases. We investigated the effect of oral administration of Bifidobacterium bifidum G9-1 (BBG9-1) on immunoglobulin (Ig) E production in BALB/c mice. Live BBG9-1 was orally administered to mice for 2 weeks from 1 week before ovalbumin (OVA)-immunization. The treatment of BBG9-1 significantly reduced serum total IgE level. In addition, BBG9-1 significantly and largely reduced the serum level of OVA-specific IgE without lowering of the specific IgG1 and increasing of the specific IgG2a. We also examined T helper type (Th) 1 and Th2 cytokine production from OVA-immunized splenocytes by restimulation with OVA in vitro. Productions of interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 from the splenocytes of mice given BBG9-1 were weaker than those of control mice. We conclude that oral administration of BBG9-1 selectively and powerfully suppresses total and antigen specific IgE production in mice. It is suggested that BBG9-1 is useful for the prophylactic treatment in IgE-dependent allergic diseases.

Oral administration of Bifidobacterium bifidum G9-1 suppresses total and antigen specific immunoglobulin E production in mice.

Previous studies using experimental animal models have reported the beneficial effects of probiotics on allergic responses; however, their long-term effects on allergic nasal symptoms in clinical settings have not yet been elucidated in detail. In the present study, a guinea pig allergic rhinitis model involving repeated inhalation challenges with a natural allergen, Japanese cedar pollen, was used to examine the longitudinal effects of Bifidobacterium bifidum G9-1 (BBG9-1) on allergic nasal symptoms. BBG9-1 was administered orally once a day. Amelioration of nasal blockage was consistently observed throughout the experimental period in the BBG9-1-treated group. Although challenge-induced sneezing was not significantly inhibited in the BBG9-1-treated group, prolonged treatment with BBG9-1 slightly reduced the frequency of sneezing. Antigen-specific IgE antibody production was also not inhibited in the BBG9-1-treated group. Increases in the numbers of eosinophils and neutrophils in nasal cavity lavage fluid collected after pollen challenge were almost completely suppressed by BBG9-1 treatment, whereas those in mast cell mediators, histamine and cysteinyl leukotrienes were not. In contrast, increases in the levels of nitric oxide metabolites were potently suppressed. Furthermore, prolonged BBG9-1 treatment markedly suppressed exogenous leukotriene D4 -induced nasal blockage. Thus, prolonged oral administration of BBG9-1 suppresses Japanese cedar pollen-induced allergic nasal symptoms. The inhibitory mechanisms responsible may involve reductions in the responsiveness of target organs, such as endothelial cells in nasal mucosal blood vessels, to chemical mediators.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1348-0421.12324

Longitudinal study of effects of oral dosage of Bifidobacterium bifidum G9-1 on Japanese cedar pollen-induced allergic nasal symptoms in guinea pigs.

Recent studies of several animal models have shown beneficial effects of probiotics against allergic responses. However, few reports have examined the effects of probiotics on allergic nasal symptoms such as sneezing and nasal obstruction in animal models of allergic rhinitis. This study evaluated the efficacy of Bifidobacterium bifidum G9-1 (BBG9-1) on antigen-induced nasal symptoms using guinea pig models of allergic rhinitis. Oral administration of BBG9-1 significantly inhibited antigen-induced allergic nasal reactions such as sneezing and nasal obstruction. Our results suggest that BBG9-1 may be useful for alleviating nasal symptoms in patients with allergic rhinitis.

/pdf/effects-of-bifidobacterium-bifidum-g9-1-on-nasal-symptoms-in-12ferck92y.pdf

Effects of Bifidobacterium bifidum G9-1 on Nasal Symptoms in a Guinea Pig Model of Experimental Allergic Rhinitis

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Oral administration of Bifidobacterium bifidum G9-1 suppresses total and antigen specific immunoglobulin E production in mice.

Longitudinal study of effects of oral dosage of Bifidobacterium bifidum G9-1 on Japanese cedar pollen-induced allergic nasal symptoms in guinea pigs.

Effects of Bifidobacterium bifidum G9-1 on Nasal Symptoms in a Guinea Pig Model of Experimental Allergic Rhinitis