Lactiplantibacillus plantarum GMNL-661 Ameliorates Clostridioides difficile Infection and Reconfigures Intestinal Microbiota in a Murine Model

Clostridioides difficile infection (CDI) is a significant global health threat, often resulting from antibiotic-induced disruption of the gut microbiota, which leads to severe gastrointestinal issues. Current treatments, such as vancomycin, are effective but can cause subsequent relapses, further microbiota disruption, and high treatment costs. Probiotics offer a promising microbiota-based therapeutic strategy. Following an in vitro screening for novel lactic acid bacterial (LAB) strains with strong anti-C. difficile ability and good tolerance to digestive challenges, Lactiplantibacillus plantarum GMNL-661 emerged as a potential solution to combat CDI. In a CDI mice model, the appropriate dose of GMNL-661 effectively alleviated CDI, which caused weight loss, gut inflammation, and mucin depletion. GMNL-661 alleviated CDI symptoms through increased gut barrier genes and downregulated IL-1 and IL-18. 16s rDNA analysis of mice stool from CDI and CDI supplemented with GMNL-661 showed distinct microbiota ecology. GMNL-661 dramatically affected the microbiome of CDI, increasing Lactobacillus spp. and Clostridium cluster XVIII while reducing Clostridium and Enterococcus species. Genome analysis of GMNL-661 revealed minimal safety concerns in antibiotic resistance and virulence genes, confirming that it is suitable for inclusion in the food chain. Antimicrobial peptide (AMP) prediction on GMNL-661 and 299v genome suggested a strong potential candidate for anti-CD antimicrobial peptides. These findings highlighted L. plantarum GMNL-661 as an effective and highly safe therapeutic agent against CDI in clinical.