The allergic reaction mechanism of Nisin

I. Mechanisms of Nisin Allergic Reactions

As a natural polypeptide preservative (containing 34 amino acid residues) produced by lactic acid bacteria, Nisin's allergic reaction mechanisms are closely related to the immune recognition process of protein allergens, which can be analyzed at the following levels:

1. Immune Recognition and IgE-Antibody Mediated Allergic Reactions

Nisin's polypeptide structure may be recognized by the human immune system as a "foreign antigen". When the body first encounters Nisin, antigen-presenting cells (e.g., dendritic cells) ingest and process it, presenting antigenic epitopes to T helper cells (Th cells), which in turn induce B cells to produce specific immunoglobulin E (IgE) antibodies. These IgE antibodies bind to FcεRI receptors on the surface of mast cells and basophils, sensitizing the body. Upon re-exposure to Nisin, it crosslinks with cell-surface IgE antibodies, triggering degranulation of mast cells and basophils to release inflammatory mediators like histamine and leukotrienes, causing immediate allergic reactions (Type I hypersensitivity) such as urticaria, dyspnea, and hypotension.

2. Potential for Cross-Allergy

Nisin's amino acid sequence may share structural similarity with certain natural proteins (e.g., casein and whey protein in dairy products, or proteins of lactic acid bacteria themselves), leading to cross-allergy. For example, individuals allergic to dairy products may exhibit cross-reactions to Nisin due to homologous antigenic epitopes with milk proteins. Additionally, residual lactic acid bacteria bacterial proteins or fermentation by-products in Nisin production may act as contaminant antigens to induce allergies.

3. Non-IgE Mediated Allergic Reactions (Delayed Reactions)

Beyond IgE-mediated immediate reactions, Nisin may trigger allergies through non-IgE dependent mechanisms, such as activating the complement system, inducing cytokine release, or directly stimulating mast cell degranulation. These reactions typically have a slower onset, with symptoms like rashes or gastrointestinal discomfort. The mechanisms are more complex and currently less studied.

4. Influence of Individual Differences and Immune Status

Allergic reactions exhibit significant individual variations, related to genetic factors (e.g., HLA gene polymorphism), immune system maturity (e.g., infants with incomplete intestinal barrier function are more susceptible to sensitization), and gut microbiota balance. Individuals with immune dysfunction or in an inflammatory state may be more sensitive to Nisin's immune recognition, increasing allergy risk.

II. Preventive Strategies for Nisin Allergic Reactions

Preventive measures against potential Nisin allergic reactions can be taken at the levels of food production, labeling, consumer education, and clinical management:

1. Optimizing Production Processes to Reduce Allergen Residues

Upgraded Purification Technologies: During Nisin production, fine purification processes like chromatography and membrane filtration reduce residues of lactic acid bacteria bacterial proteins, fermentation medium components (e.g., casein hydrolysates), and other impurities, minimizing allergenic risks from contaminant antigens.

Fermentation Condition Control: Optimizing lactic acid bacteria fermentation parameters (e.g., temperature, pH, medium composition) reduces the generation of Nisin structural variants or degradation products, avoiding new allergenic epitopes.

2. Strict Labeling and Allergen Warnings

Clear Ingredient Labeling: Clearly mark "contains Nisin" or "produced by lactic acid bacteria fermentation" on food labels to help consumers with allergies identify them. For products with potential cross-allergy to other proteins (e.g., dairy, soy), add warnings (e.g., "This product contains Nisin, which may cause cross-reactions in individuals allergic to dairy products").

Implementing Allergen Management Systems: Food enterprises should follow international allergen management standards (e.g., EU EC 1169/2011 regulations), establishing a full-process allergen control flow from raw material procurement to finished product delivery to prevent cross-contamination of Nisin with other allergens.

3. Developing Hypoallergenic Nisin or Alternative Solutions

Molecular Modification and Structure Optimization: Using genetic engineering or chemical modification technologies to alter Nisin's antigenic epitopes, reducing its immunogenicity while retaining antibacterial activity. For example, site-directed mutagenesis of amino acid sites in Nisin prone to immune recognition decreases IgE antibody binding probability.

Alternative Composite Preservative Systems: For high-allergy-risk foods (e.g., infant foods), adopt compounding schemes with natural antibacterial components (e.g., tea polyphenols, chitosan, natamycin) to reduce dependence on Nisin and lower allergenic risks.

4. Strengthening Consumer Education and Clinical Monitoring

Science Popularization: Through food regulatory agencies, medical institutions, or media channels, educate consumers about Nisin's origin, uses, and allergy risks, enhancing self-protection awareness among allergic individuals (e.g., reading labels, avoiding repeated exposure to Nisin-containing foods).

Clinical Diagnosis and Management: For Nisin suspected Nisin allergy patients, confirm diagnosis via skin prick tests, serum specific IgE detection, etc., and have doctors formulate personalized avoidance plans. Severe allergy sufferers should carry adrenaline auto-injectors to prevent sudden allergic reactions.

5. Risk Assessment and Dynamic Regulation

Regulatory authorities should update Nisin safety assessment standards regularly based on the latest toxicological and allergological research data, set reasonable acceptable daily intake (ADI), and require enterprises to conduct allergenic risk assessments for new products to control allergy hazards at the source.

Nisin's allergic reaction mechanisms mainly involve IgE-mediated immune recognition, cross-allergy, and individual immune differences, while preventive strategies must span production, labeling, consumption, and medical care. With technological advancements and regulatory improvements, Nisin can be more widely applied in food preservation while ensuring safety.