Dietary fiber reduces mortality from secondary bacteremia in a murine model of antibiotic-induced Clostridioides difficile infection

Despite antibiotic stewardship and improved sanitation, Clostridioides difficile infection (CDI) remains a major public health problem. Dietary modulation is promising for prevention. Using a murine model of antibiotic-induced CDI, we show that mice fed low-fiber diets with both high- and low-fat content had high mortality, but this effect was ameliorated with fiber supplementation. We found increased presence of intestinal pathobionts, including Escherichia and Enterococcus, in blood, liver, and spleen in mice on low-fiber diets, suggesting bacteremia as a cause of mortality. Despite higher mortality, mice fed a high-fat/low-fiber diet did not have higher cecal TcdA/B toxin levels and had less cecal and colonic inflammation 3 days after C. difficile inoculation. These mice also had a delayed onset of morbidity compared to the other diets. Our data suggests dietary fiber promotes an appropriate immune response to CDI that can protect from secondary infections, and that fiber intake could reduce complications of CDI.