The Beneficial Effects of a Combination of Prebiotics and Bacterial Consortium on Clostridioides difficile Infection in a Mouse Model

Objectives: Galacto-oligosaccharides (GOS) are prebiotics that are metabolized by the microbes in the gut to confer beneficial effects to the host. GOS have been shown to protect against pathogen infections by structurally mimicking intestinal binding sites and preventing epithelial barrier dysfunction. Its anti-adhesive properties have been shown to inhibit Escherichia coli and Salmonella enterica serovar Typhimurium-associated enteric infections. The goal of this study was to explore the effects of GOS, along with a beneficial bacterial consortium or fecal microbiota transplantation (FMT) in a mouse model of Clostridioides difficile (C. difficile) infection. Methods: C57BL/6J mice(4–6 weeks old) were given either a Control or GOS diet, received either the bacterial consortium or FMT and were infected with C. difficile R20291. Intestinal permeability was determined by measuring FITC-dextran concentrations in serum at the end of the experiment and C. difficile clearance over time was determined by qPCR. Microbiome analysis was conducted via 16S rRNA amplicon sequencing. Results: The GOS diet favored the resistance to C. difficile colonization but did not impact clearance rates. Mice that received the bacterial consortium and FMT had increased permeability but a lower abundance of C. difficile at the end of the study. Conclusions: Our results suggest that GOS supplementation may create an environment that aids in the prevention of pathogen colonization, leading to future clinical interventions to explore prebiotic supplementation as a preventative treatment for infection. Funding Sources: UNC Microbiome Core, Center for Gastrointestinal Biology and Disease (CGIBD), Nutrition Obesity Research Center (NORC).