Impact of nisin on Clostridioides difficile and microbiota composition in a faecal fermentation model of the human colon

Aims Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota. Methods and Results Faecal slurries were prepared from fresh faecal samples and spiked with C. difficile (10(6) CFU per ml). Nisin was added to each fermentation at a range of concentrations from 0 to 500 mu M. Following 24 h, 16S rRNA gene sequencing was performed, and the presence of viable C. difficile was assessed. There was no viable C. difficile detected in the presence of 50-500 mu M nisin. There was a decrease in the diversity of the microbiota in a nisin dose-dependent manner. Nisin predominantly depleted the relative abundance of the Gram-positive bacteria whilst the relative abundance of Gram-negative bacteria such as Escherichia Shigella and Bacteroides increased. Conclusions Using an ex vivo model of the colon, this study demonstrates the ability of purified nisin to selectively deplete C. difficile in a faecal microbial environment and establishes the minimum concentration at which this occurs whilst having a minimal impact on the composition of the microbiota. Significance and Impact of the Study This study opens up the potential to use nisin as a therapeutic for clostridial gut infections.