To extend the shelf life of food, manufacturers often add preservatives to their products. These substances are designed to eliminate microorganisms that can cause food to spoil. While traditional preservatives like sugar, salt, vinegar and alcohol have a long history of use, modern food labels often list more obscure additives like sodium benzoate, calcium propionate and potassium sorbate. Research into a food preservative widely used for its ability to destroy pathogens shows that it can also affect beneficial bacteria, posing a risk to the balance of the gut microbiome.
Bacteria produce chemicals called bacteriocins to kill microbial competitors. These chemicals act as natural preservatives by killing potentially dangerous pathogens in food. Lantibiotics are a class of bacteriocins with particularly strong antibacterial properties and are widely used by the food industry.
Despite the widespread use of Lantibiotics, little is known about how these biotins affect the gut microbiome of those who consume them. The microbes in the gut live in a delicate balance, with commensal bacteria providing important benefits to the body by breaking down nutrients, producing metabolites and – importantly – defending against pathogens. If too many commensal bacteria are killed indiscriminately by antimicrobial food preservatives, opportunistic pathogenic bacteria may take over and wreak havoc—with results that are no better than eating contaminated food in the first place.
A new study published in the journal ACS Chemical Biology by scientists at the University of Chicago found that Lantibiotics, the most common class of biological agents, have a strong inhibitory effect on pathogens and intestinal commensal bacteria that maintain human health.
Nisin is a commonly used fungicide in everything from beer and sausage to cheese and dips. It is produced by bacteria living in the mammary glands of cows, but microbes in the human gut also produce similar biocides. Zhenrun "Jerry" Zhang, PhD, a postdoctoral scholar in the laboratory of Eric Pamer, MD, Donald F. Steiner Professor of Medicine at the University of Chicago and director of the Duchosos Family Institute, wanted to study the effects of this naturally occurring biotin on commensal gut bacteria.
"Essentially, Nisin is an antibiotic that has long been added to our food, but how it affects our gut microbes has not been well studied," Zhang said. "While it may be very effective in preventing food contamination, it may also have a greater impact on our body's gut microbes."
He and his colleagues mined a public database of human gut bacterial genomes and discovered genes that produce six different gut-derived lantibiotics that are very similar to Nisin, four of which are novel. They then worked with Wilfred A. van der Donk, Ph.D., the Richard E. Hector Professor of Chemistry at the University of Illinois at Urbana-Champaign, to produce different versions of these antibiotics to test their effects on pathogens and commensal gut bacteria. The researchers found that while different Lantibiotics had different effects, they were equally effective at killing pathogens and common bacteria.
Zhang said: "This study shows for the first time that intestinal commensal bacteria are susceptible to Lantibiotics, sometimes even more sensitive than pathogens. Judging from the current content of Lantibiotics in food, they are likely to affect our intestinal health as well."
Zhang and his team also studied the structure of Lantibiotics to better understand their activity and therefore how their antimicrobial properties could be harnessed for good. For example, in another study, the Palmer lab found that a consortium of four microbes, including one that produces lantibiotin, helped protect mice from antibiotic-resistant enterococci. They are also studying the prevalence of rand-biotin-resistant genes in different populations to better understand how this type of bacteria colonizes the gut under different conditions and diets.
"It appears that Lantibiotics and their derived strains are not always beneficial to health, so we are looking for ways to offset potential adverse effects while taking advantage of their more beneficial antimicrobial properties," Zhang said.