Bacteria produce chemicals called bacteriocins to kill microbial competitors, and some of these chemicals are used as natural preservatives to kill potentially dangerous pathogens in food, making food safer.
Lanthipeptides, also known as lantibiotics, are a class of bacteriocins that have especially potent antimicrobial properties and they are widely used by the food industry for their food preservation properties.
Nisin (E 234) is one such lantibiotic that is approved food additive in the EU. In 2017, scientists at the European Food Safety Authority (EFSA) greenlighted extending its use in unripened cheese at a maximum level of 12 mg/kg and in heat-treated meat products at a maximum level of 25 mg/kg, concluding that this would not be of safety concern.
However, a study published in the peer-reviewed journal ACS Chemical Biology found that nisin, used in products ranging from beer and sausages to cheese and dipping sauces, and nisin-like preservatives may disrupt gut bacteria.
With funding from the GI Research Foundation, the team of researchers, led by Zhenrun Zhang from the University of Chicago, produced six different gut-derived lantibiotics that closely resembled nisin, four of which were new. They then tested their impact on both “good” and “bad” microorganisms: pathogens and commensal gut bacteria.
The scientists found that while the effects of the different lantibiotics varied, all of them killed both pathogens and commensal bacteria alike.
Lead researcher: Nisin ‘is in essence an antibiotic’
“Microbes in the gut live in a delicate balance, and commensal bacteria provide important benefits to the body by breaking down nutrients, producing metabolites, and – importantly – protecting against pathogens,” the researchers said in a statement.
“If too many commensals are indiscriminately killed off by antimicrobial food preservatives, opportunistic pathogenic bacteria might take their place and wreak havoc – a result no better than eating contaminated food in the first place.”
Zhang, a postdoctoral researcher and lead author of the study, said that nisin, which is in essence an antibiotic, has been added to food for a long time but its impact on gut microbes is not well studied.
“Even though it might be very effective in preventing food contamination, it might also have a greater impact on our human gut microbes,” he said, adding that this study was one of the first to show that gut commensals are susceptible to lantibiotics – and are sometimes even more sensitive than pathogens.
“With the levels of lantibiotics currently present in food, it’s very probable that they might impact our gut health as well,” he said.
Implications for clean-label reformulation
The findings are likely to be unwelcome news for manufacturers looking to use natural preservatives, such as nisin, to keep their products’ ingredient lists clean.
Carole Bingley is senior associate principal scientist at Reading Scientific Services Ltd (RSSL), a scientific consultancy that accompanies manufacturers in new product development (NPD). She said RSSL has seen a rise in requests from manufacturers looking to reformulate to reduce certain additives due to concerns over the impact on the microbiome.
“At the moment we’re not seeing anything beyond the usual requests for clean label. It will be interesting to see how the evidence builds for additives and the microbiome, but my experience is that companies are keen to minimise the use of additives as much as possible, particularly for NPD projects.”
She added: “Reformulation to remove or replace additives is a bigger challenge because of any impact on the processability, eating quality, or shelf life.”
Microbiome research, noise, and marketing
In any case, more research in needed to understand the impact of preservatives and other additives on gut microbiota.
According to a February 2024 review, published in the journal Nature Reviews: Gastroenterology & Hepatology, some preclinical studies have shown that food additives commonly added to ultra-processed foods (UPFs), such as emulsifiers, sweeteners, colours, microparticles, and nanoparticles, can affect gut health parameters, including the microbiome, intestinal permeability, and intestinal inflammation.
However, there have been few human intervention studies on the effect of UPFs or additives on gut health and disease, the reviewers noted.
One small randomised controlled trial led by Kevin Hall involving 20 patients demonstrated that consumption of UPFs resulted in both increased energy intake and body weight when compared with a calorie- and macronutrient-matched unprocessed diet, but no clinical studies to date have investigated the effect of UPFs on gut health or disease.
Establishing causality in diet-related studies is notoriously difficult – particularly when trying to determine a link between the impact of one specific food additive and the gut microbiome because even a healthy gut microbiome is constantly in flux.
“Loads of trials report that a diet or ingredient ‘changed the microbiome’. What’s the problem with that? The microbiome changes all the time,” wrote Dr Nicola Guess, clinical and academic dietitian and research fellow at the University of Oxford and King’s College London, on her online blog.
Guess added: “[…T]he most we know is that a high-fibre, unprocessed diet is the best thing you can do for your microbiome and metabolic health. Right now, the rest is just noise and marketing.”
The scientists behind the nisin study are continuing their research in this field and are also studying the prevalence of lantibiotic-resistant genes across different populations of people. They hope to better understand how such bacteria can colonise the gut under different conditions and diets.
“It seems that lantibiotics and lantibiotic-producing bacteria are not always good for health, so we are looking for ways to counter the potential bad influence while taking advantage of their more beneficial antimicrobial properties,” Zhang said.
