Nisin, an antimicrobial agent which is produced by a naturally occurring bacterium, has been studied since the 1950s and has traditionally been used as a food preservative. However, according to a recent University study, nisin has been found to interact with and negatively affect the growth of some types of cancer as well as antibiotic-resistant bacteria.

Dentistry Prof. Yvonne Kapila, lead researcher for the study, said the bacteria has been accepted as a safe method of food preservation by both the World Health Organization and the Food and Drug Administration.

“Of all the food preservatives that are out there, nisin is widely, widely used and it’s the bacteriocin that has had the most background in terms of knowledge,” Kapila said.

The bacterium was first identified on certain cheeses, Kapila said. Many of the cheeses that contained traces of nisin were being presented, which led to the idea that there had to be an active, preserving component to nisin.

“It’s been around a long time and there’s a large margin of safety and I think that’s what makes it very attractive (to consumers) — that it’s been used as a food preservative and it’s been used for many, many years in the food industry,” Kapila said.

Kapila’s research into nisin began a few years ago, with a post-doctoral student who was working to purify other types of bacteriocins prior to coming to her lab. Bacteriocins, which are toxins produced by bacteria to stop the growth of similar bacterial strains, showed cytotoxicity to some tumor cells, meaning they’re toxic to certain types of cancers.

When she and the other researchers tested nisin on head and neck cancer cells, they found that it induces cancer cell death. In contrast, when tested on normal control cells to see if they were affected, they showed no impact, prompting the study.

Rackham dentistry student Jae Shin, co-author of the study, said he investigated the nisin’s role with regard to pathogens in dental plaque.

“What we found is that the nisin we used, the highly purified and processed form of nisin, shows an inhibition effect on many of the oral pathogens found in dental plaque,” Shin said. “We also found that nisin can inhibit the formation of dental plaque biofilms and also alter or disrupt the already-formed mature biofilms.”

Kapila said an animal model was used for the study where tumor cells were injected into mice. Once the tumors were visible, researchers began to feed the animals a nisin shake.

After a period of three weeks, the control animals had large tumors, while those treated had an average of a 70 percent reduction in the tumor cells, as well as a 90 percent reduction in the tumors themselves.

Kapila said there are also other models that she and the researchers have used to test nisin. In another model, the researchers fed a risin to separate group of mice because they had to kill the control mice. For ethical reasons, because the mice suffer after the tumors get so large, researchers cannot keep the mice alive. However, for the subset of mice that were treated with the nisin, their lifespans were extended.

“The nisin-treated mice were kept alive — the longest one was up to four months,” Kapila said. “That’s using the model where we’ve already injected the tumor cells, the tumors were already present and we’re just feeding the mice the nisin to keep them alive.”

Kapila said the researchers have also done another pilot research project where they fed the mice an older formulation of nisin — with only a 2.5 percent concentration — before the tumor cells were injected.

Shin said the new formulation of nisin, Nisin ZP, is about 95 percent pure and is a naturally occurring variant of nisin. The only difference between the two nisin types is the inclusion of ZP, a highly purified form of nisin, as opposed to some other commercially available forms of nisin, which are concentrated at 2.5 percent. Kapila said the ZP is the most effective.

Kapila said they are currently working to see if the bacteriocin could be toxic to cancers in other areas of the body aside from head and neck cancer cells. She said it would be beneficial to try to do the experiment and feed the mice the nisin milkshake prior to injecting them with the tumor cells to see if they can prevent the cells from initially even taking root.

Ultimately, Kapila said she is hoping to do a clinical trial, but finding funding has been a setback.

Though the research suggests that nisin could help prevent the development of cancer cells, this does not mean overconsumption of products that contain preservatives such as nisin will be beneficial to one’s health. One common misconception is that over-consuming products that contain these and other similar preservatives will have positive effects and reduce the likelihood of developing cancer cells. This is not true, Kapila said.

“The preservative that’s in the food, there is a shelf life to it,” Kapila said. “So by the time people ingest foods that have nisin in it, a lot of it is probably broken down. So the amount of it that people actually ingest is not anywhere near to the quantities that have been tested in the animal models or the cell models.” 

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