Gut microbiome: temporary shift in bacteria
A 2023 study in pigs found that nisin consumed at realistic dietary levels reached the lower intestine intact and reduced populations of Gram-positive bacteria, particularly Lactobacillus species, while Gram-negative bacteria including E. coli increased. Short-chain fatty acid production, which beneficial gut bacteria generate from fibre, also fell during treatment. Crucially, all changes reversed within ten days of stopping nisin, and overall bacterial diversity remained stable. No equivalent controlled study has yet been carried out in humans.
Pig model study found nisin reversibly reduced Gram-positive gut bacteria including Lactobacillus and Bifidobacterium, with corresponding decreases in acetate (40%) and butyrate (66%) production; changes resolved within ten days of treatment ending.
2023AnimalModulation of the gut microbiome with nisin, Scientific Reports
Antimicrobial resistance: an open question
Nisin acts on a bacterial target, Lipid II, that differs from the targets of conventional clinical antibiotics. Stable resistance to nisin is rarely observed in practice and, despite decades of food use, no widespread emergence of nisin-resistant strains has been reported. However, the 2017 EFSA panel explicitly declined to evaluate whether dietary nisin exposure could select for antimicrobial resistance or cross-resistance with other agents, and called for that question to be assessed separately. That assessment had not been published at the time of writing.
EFSA's 2017 safety panel noted that potential induction of antimicrobial resistance by dietary nisin and its modulating effect on gut microbiota were deliberately not evaluated and recommended a separate assessment of these risks.
2017Regulatory reviewEFSA Panel on Food Additives and Nutrient Sources (ANS), EFSA Journal 2017;15(12):5063
Despite decades of food industry use, nisin resistance in clinically relevant bacteria has not emerged at a population level, partly because nisin targets Lipid II rather than protein synthesis pathways targeted by conventional antibiotics.
2023ObservationalAfter a century of nisin research - where are we now?, FEMS Microbiology Reviews
Toxicology: no adverse effects at food-relevant doses
The key toxicology study was a 90-day rat feeding trial. The highest dose tested, 225mg nisin per kg of body weight per day, produced no adverse effects, establishing that as the no-observed-adverse-effect level. EFSA applied a 200-fold safety factor to account for species differences and the subchronic duration of the study, arriving at an ADI of 1mg/kg body weight per day. Estimated dietary exposure from all permitted uses falls well below that figure across all population groups. No genotoxicity was identified in the available data.
90-day rat feeding study identified a NOAEL of 225mg nisin/kg body weight per day, the highest dose tested; no adverse effects or genotoxicity were found.
2017AnimalEFSA Panel on Food Additives and Nutrient Sources (ANS), EFSA Journal 2017;15(12):5063
EFSA revised the ADI upward from 0.13mg to 1mg nisin/kg body weight per day following the new subchronic toxicity data; estimated dietary exposure from all permitted uses was below the new ADI for all population groups.
2017RegulatoryEFSA Panel on Food Additives and Nutrient Sources (ANS), EFSA Journal 2017;15(12):5063