On Lactococcus lactis UL719 competitivity and nisin (Nisaplin®) capacity to inhibit Clostridium difficile in a model of human colon

Abstract

Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomially acquired, antibiotic-associated diarrhea and pseudomembranous colitis. Although metronidazole and vancomycin were effective, an increasing number of treatment failures and recurrence of C. difficile infection are being reported. Use of probiotics, particularly metabolically active lactic acid bacteria, was recently proposed as an alternative for the medical community. The aim of this study was to assess a probiotic candidate, nisin Z-producer Lactococcus lactis UL719, competitivity and nisin (Nisaplin®) capacity to inhibit C. difficile in a model of human colon. Bacterial populations was enumerated by qPCR coupled to PMA treatment. L. lactis UL719 was able to survive and proliferate under simulated human colon, did not alter microbiota composition, but failed to inhibit C. difficile. While a single dose of 19 μmol/L (5× the MIC) was not sufficient to inhibit C. difficile, nisin at 76 μmol/L (20×the MIC) was effective at killing the pathogen. Nisin (at 76 μmol/L) caused some temporary changes in the microbiota with Gram-positive bacteria being the mostly affected. These results highlight the capacity of L. lactis UL719 to survive under simulated human colon and the efficacy of nisin as an alternative in the treatment of C. difficile infections.

Advances in the Microbiome: Applications to Clostridium difficile Infection

“…Nisin has also been shown to be effective at killing C. difficile in a model human colon, albeit at high concentrations (20 times the MIC; 76 µmol/L). However, the higher concentration was also associated with undesirable alterations to the commensal microbiota, with reductions in Ruminococcaceae , Lachnospiraceae , Lactobacillaceae/Leuconostocaceae and bifidobacteria [ 132 ].…”

Impact of microbiome-based interventions on gastrointestinal pathogen colonization in the intensive care unit

“… 101 Similar results have been found in the ability of bacteriocin-producing bacteria to inhibit various Streptococcus species, 102 Salmonella enteritidis , 103 Listeria monocytogenes , 104 and Clostridioides difficile. 105 – 107 …”

Mechanistic Insights in the Success of Fecal Microbiota Transplants for the Treatment of Clostridium difficile Infections

“…Nisin is a bacteriocin with broad antimicrobial activity against a wide range of gram-positive bacteria ( Lubelski et al, 2008 ). It can be isolated from the known gut residents such as Blautia obeum A2-162 ( Hatziioanou et al, 2017 ) and species that can proliferate in conditions that resemble the gut, including Lactococcus lactis UL719 ( Le Lay et al, 2015 ). In vitro studies show that nisin can inhibit spore germination and vegetative growth of C. difficile ( Le Lay et al, 2016 ).…”

“…In vitro studies show that nisin can inhibit spore germination and vegetative growth of C. difficile ( Le Lay et al, 2016 ). In a human colon model, L. lactis UL719 did not significantly alter the microbiota composition and was not effective against C. difficile , likely because nisin produced in vivo does not reach inhibitory levels ( Le Lay et al, 2015 ).…”