ReviewImmunoregulatory and immunostimulatory responses of bacterial lysates in respiratory infections and asthma
Introduction
In light of the increasing prevalence of non-communicable diseases, the “hygiene hypothesis” postulated by Strachan1 pointed out the evolutionary necessity of contact between the host and environment. Pioneering works by several groups have since provided support for the relation between living in cleaner environments and the development of allergic sensitization and asthma.[2], [3], [4] These groups also hypothesized that infancy—when immune system development takes place—is a crucial period during which allergic phenotypes surface, and that increasing exposure to microbial antigens during this period can lower the risk of atopy.4 It has been found that the ingestion of probiotic bacteria during pregnancy and continued probiotic consumption during the postnatal period by the infant can decrease the risk of developing atopic dermatitis and food hypersensitivity at older ages.5
Although the ingestion of viable commensal bacteria can affect the development of allergic airway diseases, there is evidence to suggest that bacteria-derived cellular extracts (ie, bacterial lysates) can stimulate and modulate lung immunity through local and systemic pathways.[6], [7] Bacterial lysates have been used to decrease recurrent respiratory tract infections in otherwise healthy children and in adults with chronic obstructive pulmonary disease (COPD), and their oral ingestion has been shown to decrease the number of virus-induced wheezing episodes in children with asthma.8 Remarkably, these preparations also have preventative effects on food sensitization and eczema in children.[9], [10] This review highlights the current understanding of how bacterial lysates modify immune responses and discusses their effectiveness in enhancing immunity in the respiratory tract.
Section snippets
Bacterial Lysate Composition and Locoregional Effects
Bacterial lysates exist as mechanically fractioned particulates or chemically degraded lyophilized cells derived from pathogenic bacterial strains responsible for respiratory tract infections. OM-85 BV (also known as Broncho-Vaxom, Broncho-Munal, Ommunal, Paxoral, and Vaxoral) is the most frequently cited of these compounds and contains extracts derived from 8 bacterial species (Staphylococcus aureus, Streptococcus viridans, Streptococcus pyogenes, Diplococcus pneumoniae, Klebsiella pneumoniae,
Interaction of Bacterial Lysates with Pattern Recognition Receptors
The protective role of specific or polyclonal IgA does not explain the protection achieved in experimental animals treated with bacterial antigens and then challenged with completely different pathogens. For example, rodents treated with H influenzae–derived bacterial lysates showed an enhanced immune response to challenges by influenza A,[11], [28] Streptococcus pneumoniae,29 and Aspergillus fumigatus.30 In mice infected with H1N1 influenza virus and Salmonella typhimurium, bacterial lysates
Clinical Outcomes of Bacterial Lysate Therapy in Childhood Respiratory Diseases
Persistent lung tissue inflammation during childhood can affect lung maturation and predispose to chronic airway disease.40 Acute respiratory tract infections account for a large percentage of pediatric illnesses, many of which are self-limiting viral infections that do not require additional follow-up. The incidence of these infections can be very high; it is estimated that up to 25% of children younger than 1 year and 18% of those 1 to 4 years old are affected by recurrent respiratory
Clinical Outcomes of Bacterial Lysate Therapy in Adult Respiratory Tract Diseases
The effectiveness of bacterial lysate therapy also has been investigated in adults. The Canadian Prevention of Acute Respiratory Infection by an Immunostimulant (PAR-IS) study was a randomized, double-blinded, placebo-controlled trial that assessed whether daily ingestion of OM-85 BV could prevent acute exacerbation of adult COPD. Although the treatment did not decrease the number of acute episodes, it shortened hospitalization by 50% (1.5 vs 3.4 days) and decreased the risk of hospitalization
Applications in Allergy and Asthma
The dysregulation of regulatory T-cell lineages and TH1 and TH2 populations causes undesirable inflammatory responses against self-antigens, gastrointestinal flora, and allergens, contributing to epidemics of non-communicable diseases and autoimmune and allergic phenomena, respectively.[40], [59] Regulatory T cells secrete IL-10 and TGF-β and are present in smaller numbers in individuals with atopy. Bacterial lysates promote TGF-β–mediated development of regulatory T-cell subsets,[14], [22],
Are Bacterial Lysates Safe to Use?
Immunostimulant treatment is limited by the difficulties in obtaining high-quality data and patient safety concerns. The aforementioned Cochrane review found no differences in the frequency of adverse events between immunostimulant-treated and control groups,45 and another study failed to find differences in adverse cutaneous and gastrointestinal reactions in COPD between patients treated with bacterial lysates and those receiving a placebo. A prospective RCT of 54 children younger than 12
Conclusion
Bacterial lysates are used to prevent recurrent respiratory tract infections and acute exacerbation of COPD, although little is currently known about the molecular mechanisms underlying their clinical effects. The most plausible explanation is an IgA antibody response against pathogens at mucosal surfaces and activation of mucosal DCs by TLR-dependent signaling through TLR-2/6 and TLR-9. In addition to proinflammatory cytokine secretion, these mechanisms might provide antiviral coverage.
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2022, Medicine in MicroecologyCitation Excerpt :Bacterial lysates are a product of alkaline proteolysis for the following bacteria: Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae, Klebsiella ozaenae, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus viridans and Moraxella catarrhalis. Other than eradicating pathogens, bacterial lysates were shown to have pleiotropic immunomodulating effects on both the innate and adaptive immune responses [13]. It can enhance the activity of immune cells by stimulating mucosa-derived lymphoid tissue [14,15].
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Disclosure: Dr Feleszko has received speaker's honoraria from GSK, Pierre-Fabre Medicament, Ranbaxy, and UCB. The other authors declare no conflicts of interest.