Efficacy of grapefruit seed extract and lactic acid bacteria in reducing Clostridioides difficile infection via gut microbiota modulation

Antibiotic-induced dysbiosis is a key factor that causes Clostridioides difficile infection (CDI). The current first-line drugs for initial CDI are antibiotics, and finding an alternate therapy to prevent recurrent CDI is essential. In this study, the anti-C. difficile activities of two isolated probiotic strains (Pediococcus pentosaceus CD5 and Lactobacillus salivarius CD4) and grapefruit seed extract (GSE) were investigated in vitro and in vivo. Specifically, GSE inhibited the growth of C. difficile at a minimal inhibitory concentration (MIC) of 40 ppm. Similarly, live cells of the two probiotics, as well as their cell-free culture supernatants, with or without pH adjustment, substantially suppressed C. difficile growth. In a CDI mouse model, C. difficile colonization in the cecum and colon inflammation were significantly reduced by GSE, followed by the probiotic treatments. A metagenomic analysis of cecal feces revealed that GSE and probiotic treatments modulated gut microbial compositions and enhanced the relative abundances of butyrate-producing bacteria. Therefore, GSE and the novel probiotics can potentially be administered as alternative therapies to alleviate CDI by modifying the gut microbiota. •P. pentosaceus CD5 and L. salivarius CD4 were newly isolated probiotics.•The probiotics and GSE presented anti-C. difficile activities in vitro.•C. difficile colonization was reduced by GSE and the probiotics in vivo.•C. difficile-induced colitis was most significantly alleviated by GSE.•GSE and the probiotics modulated the gut microbiota in cecum.