A Gut Game Changer That Safely Alters Microbiome Composition

In a recent study published in the journal Scientific reports, researchers report that nisin, a food preservative, remains intact while traveling through the gastrointestinal (GI) tract. Here, nisin alters the functioning and composition of the gut microbiome by altering the relative abundances of Firmicutes And Proteobacteria.

Study: Modulation of the intestinal microbiome with nisin. Image Credit: nobeastsofierce / Shutterstock.com

What is nisin?

Certain bacterial species produce antimicrobial peptides known as bacteriocins which have been used in the food industry as preservatives. For example, nisin, which is produced by Lactococcus lactishas broad-spectrum bactericidal activity and has been used as a food preservative throughout the world.

Nisin is effective in controlling Gram-positive bacteria such as Clostridioides difficile. In combination with other compounds such as ethylenediaminetetraacetic acid and cinnamaldehyde, nisin has been shown to be effective in controlling enterotoxigenic Gram-negative bacteria such as Escherichia coli.

Previous studies have used chicken and mouse models to demonstrate the live efficiency of nisin on the microbiome, while the effectiveness of nisin has been proven in ex-vivo human microbiome experiments. To date, no study has assessed the live effects of nisin in large mammals.

About the study

In the present study, researchers used porcine models to elucidate the impact of orally ingested nisin on the gut microbiome using a metagenomics approach, as well as 16S ribonucleic acid (RNA) sequencing and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS). The transit of nisin encapsulated in an ethylcellulose preparation, which protects the protein from degradation in the gastrointestinal tract, through the small intestine, and its impact on the intestinal microbiome were compared with that of non encapsulated.

Piglets were fed encapsulated and non-encapsulated nisin by direct addition to pig feed. A control group was also included in the study, in which pig feed contained the ethylcellulose material used to encapsulate nisin.

Activity and MALDI-TOF MS assays were used to confirm antibacterial activity and levels of intact nisin present in faecal samples from each piglet. Fecal samples were also analyzed for concentrations of short-chain fatty acids (SCFAs) to determine gut microbiome activity levels.

The six SCFAs evaluated in this study included acetate, butyrate, isobutyric acid, isovaleric acid, propionic acid, and valeric acid. These measurements were taken at baseline, four days after treatment, and 10 days after the last treatment.

Shotgun metagenome sequencing and 16S rRNA profiling were used to assess gut microbiome composition at different time points during and after treatment. Shannon’s index was calculated to estimate the alpha diversity of piglet gut microbiomes in the three groups at baseline and at various time points after treatment. Unifrac and Bray-Curtis distances were also calculated to determine beta diversity.

Differential ranking was used to estimate the relative abundance of species after nisin treatment. Shotgun metagenomics was also used to assess the functional profile of gut microbial communities in the three groups.

Intact nisin causes reversible changes in the gut microbiome

At concentrations well below safe consumption levels, intact nisin passed through the gastrointestinal tract and altered the gut microbiome in the small intestine, thereby affecting the relative abundance of Gram-positive bacteria.

However, these changes were reversible, with gut microbiome composition returning to normal three days after discontinuation of nisin treatment. Moreover, the diversity of the gut microbiome had not changed significantly.

Nisin treatment decreased the abundance of Lactobacillus and other Gram-positive bacteria and increased the relative abundance of Gram-negative bacteria E.coli. Additionally, in groups where piglets were fed encapsulated nisin or ethylcellulose, the abundance of Catenibacterium increased, indicating that Catenibacterium the bacteria potentially used the cellulose encapsulant as an energy source.

Changes in the relative abundance of Gram-positive and Gram-negative bacteria were also reflected in butyrate, acetate, and propionate levels. To this end, nisin treatment reduced acetate and butyrate synthesis pathways and increased propionate synthesis.

conclusion

Nisin was not degraded by proteolytic enzymes in the upper gastrointestinal tract, traveled intact to the lower intestine, and altered the composition of the gut microbiome.

Nisin treatment also increased the relative abundance of Gram-negative bacteria such as E.coli and reduces the abundance of Lactobacillus and other Gram-positive bacteria. Importantly, nisin-induced changes to the gut microbiome were reversible, and gut microbiome composition was restored to prior conditions after discontinuation of nisin treatment.