May We Strengthen the Human Natural Defenses with Bacterial Lysates?

Villa, Elisa; Garelli, Valentina; Braido, Fulvio; Melioli, Giovanni; Canonica, Giorgio Walter

doi:10.1186/1939-4551-3-s2-s17

Cited by 10 publications

(13 citation statements)

References 31 publications

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“…The only differences observed were that the mechanical lysate induced higher levels of pro-inflammatory mediators in an alveolar cell line, and that the alkaline lysate required a further step of concentration during preparation to reach the same protein concentration than the mechanical. It has been suggested that PBLs prepared by mechanical disruption of the bacterial cell are more immunogenic than those prepared by chemical lysis of the cells ( 31 , 33 ). Still, here we showed that when both preparations have similar composition, they exerted similar biological effects.…”

Section: Discussionmentioning

confidence: 99%

Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation

Ferrara¹,

Rial²,

Suárez³

et al. 2021

Front. Immunol.

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Polyvalent bacterial lysates have been in use for decades for prevention and treatment of respiratory infections with reported clinical benefits. However, besides claims of broad immune activation, the mode of action is still a matter of debate. The lysates, formulated with the main bacterial species involved in respiratory infections, are commonly prepared by chemical or mechanical disruption of bacterial cells, what is believed influences the biological activity of the product. Here, we prepared two polyvalent lysates with the same composition but different method of bacterial cell disruption and evaluated their biological activity in a comparative fashion. We found that both bacterial lysates induce NF-kB activation in a MyD88 dependent manner, suggesting they work as TLR agonists. Further, we found that a single intranasal dose of any of the two lysates, is sufficient to protect against pneumococcal pneumonia, suggesting that they exert similar biological activity. We have previously shown that protection against pneumococcal pneumonia can also be induced by prior S. pneumoniae sub lethal infection or therapeutic treatment with a TLR5 agonist. Protection in those cases depends on neutrophil recruitment to the lungs, and can be associated with increased local expression of IL-17A. Here, we show that bacterial lysates exert protection against pneumococcal pneumonia independently of neutrophils, IL-17A or Caspase-1/11 activation, suggesting the existence of redundant mechanisms of protection. Trypsin-treated lysates afford protection to the same extent, suggesting that just small peptides suffice to exert the protective effect or that the molecules responsible for the protective effect are not proteins. Understanding the mechanism of action of bacterial lysates and deciphering the active components shall allow redesigning them with more precisely defined formulations and expanding their range of action.

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Section: Discussionmentioning

confidence: 99%

Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation

Ferrara¹,

Rial²,

Suárez³

et al. 2021

Front. Immunol.

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“…Microbial lysates or extracts (mostly polyvalent containing extracts of multiple species) are the products of bacterial and fungal cell lysis (cell disruption). Bacterial lysates in particular have been studied over several decades and are being used as potent immunostimulators/ immunomodulators for enhancing both innate and adaptive immunity [16][17][18][19][20][21][22]. Bacterial lysates are generally prepared by chemical (mainly alkaline cell lysis) or mechanical (lysis by high pressure shear or in bead mills) methods and they demonstrate therapeutic and prophylactic effects in the treatment of upper and lower respiratory tract infections (RTI) in both adults and paediatric patients [17][18][19][20].…”

Section: What Are Microbial Lysates and How Are They Related To The M...mentioning

confidence: 99%

“…Bacterial lysates are generally prepared by chemical (mainly alkaline cell lysis) or mechanical (lysis by high pressure shear or in bead mills) methods and they demonstrate therapeutic and prophylactic effects in the treatment of upper and lower respiratory tract infections (RTI) in both adults and paediatric patients [17][18][19][20]. In addition to their predominant use in the treatment of respiratory tract disorders like asthma, COPD and rhinitis, bacterial lysates have shown encouraging results in the treatment of various diseases like diverticulitis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, urinary tract infections, periodontitis, relapse of tuberculosis and food allergy [16][17][18][19][20][21][22]. Bacterial lysates are also effective against fungal and viral infections [23][24][25][26].…”

Section: What Are Microbial Lysates and How Are They Related To The M...mentioning

confidence: 99%

“…Most of the studies on bacterial lysates are limited to their prophylactic use [16-22, 25, 26], though they are quite effective in the management of acute episodes too [36,37]. Bacterial lysates strengthen both innate and adaptive immunity [16][17][18][19][20][21][22]. They promote broad-spectrum nonspecific innate immune response by activating the macrophages and DCs.…”

Section: How Do Microbial Lysates Work In Preventing and Alleviating ...mentioning

confidence: 99%

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Conformationally modulated immunogenic proteins in homeopathic medicines: Does protein-based mucosal immunotherapy have the potential to treat diverse diseases?

Sen¹

2022

Preprint

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The absence of any drug in the ultra-diluted homeopathic medicines coupled with unfavourable clinical trial results has painted homeopathic remedies as placebos. Different mechanisms have been forwarded to explain the anomalies but with little success. Here it is proposed that homeopathy is a form of protein-based immunotherapy and the immunogenic proteins exist in the microbial lysates, which are present in the homeopathic medicines. The microbial lysates are formed in the homeopathic medicines during their preparation, when microbes from the surrounding environment are unwittingly incorporated into the homeopathic medicines and the microbial cell lysis is induced by alcohol, a component of the drug vehicle (water-alcohol mixture), and augmented by powerful shaking. The drugs in the homeopathic medicines modulate the conformations and, in essence, the immunogenicity of the proteins present in the medicines. The modulated proteins act as immunostimulants and help in boosting and tuning both innate and adaptive immunity. In addition, bystander T cell activation and trained immunity are expected to play important roles in the therapeutic and prophylactic actions of the homeopathic medicines. The importance of dilution in homeopathy vis-à-vis the ‘law of infinitesimals’ can be appreciated by considering the effect of dilution on protein folding and the immunogenicity of proteins. In the case of ultra-diluted homeopathic medicines devoid of any drug molecule, it has been suggested that in the absence of drug-protein interaction, protein-protein interaction leads to the conformational modulation of protein molecules, where allosteric communication and synchronization of vibrating of the protein molecules play key roles. The dictum ‘like cures like’ can be understood by considering the mimicry between the antigens present on the invading pathogen and the antigens present on the proteins in the selected homeopathic medicine. The discrepancies in the clinical trial results of homeopathic medicines arising from the heterogeneities inherent in immunotherapy as well as from a strong placebo response in the clinical trials in some diseases may partly be mitigated by conducting modified clinical trials.

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“…Altogether, mechanical cell disruption has proven to be an efficient method, achieving lysis of 80-100% of the bacteria (Cazzola et al, 2012a). As other authors have previously proposed, mechanical lysates contain particles that maintain several features of intact antigenic molecules, thus providing better interaction with Toll-like receptors which is one of the initial aims of these preparations (Villa et al, 2010;Cazzola et al, 2012a,b;Esposito et al, 2018;Triantafillou et al, 2019). However, the method has the limitation of heat generation which must be minimized to avoid protein denaturalization under the process and it is more expensive than alkaline lysis.…”

Section: Proteoglycans and Ribosomesmentioning

confidence: 99%

Bacterial Lysates as Immunotherapies for Respiratory Infections: Methods of Preparation

Suárez

Ferrara

Rial

et al. 2020

Front. Bioeng. Biotechnol.

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Bacterial lysates, prepared from the microorganisms most frequently involved in human Respiratory Tract Infections (RTIs) have been in the market for several decades, and at present, several different brands are available in many countries worldwide. They all claimed to exert local and systemic immunomodulatory effects but different clinical trials show disparate results between them. The lack of consistency of predicted therapeutic effects has undermined their clinical use and hampered licensing in several countries. One explanation for such lack of consistency in the results is that their methods of preparation are also very different. Here, we review the available literature describing methods of preparation of bacterial lysates, including patent disclosure documents. We found a great variety of methodologies of preparation and a lack of standardized procedures among them. The main conclusion of our study is that there is a clear need for standardized protocols of production to obtain comparable results in clinical trials worldwide.

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May We Strengthen the Human Natural Defenses with Bacterial Lysates?

Cited by 10 publications

References 31 publications

Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation

Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation

Conformationally modulated immunogenic proteins in homeopathic medicines: Does protein-based mucosal immunotherapy have the potential to treat diverse diseases?

Bacterial Lysates as Immunotherapies for Respiratory Infections: Methods of Preparation

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