Clostridioides difficile pathogenesis and control

Clostridioides difficile infection (CDI) continues to be a notable burden worldwide, both in terms of patient mortality and morbidity, and the economic costs associated with treatment, diagnosis and management. The epidemiology of C. difficile has changed markedly over the decades, with high CDI rates driven by clinical pressures exacerbated by the severe acute respiratory syndrome coronavirus 2 pandemic, antibiotic resistance and selective pressures caused by antimicrobial use. C. difficile is challenging to diagnose and treat as it forms spores and can persist asymptomatically within the gut. Some strains express multiple virulence factors, including adhesins and toxins. The gut microbiota is crucially important in CDI, as a healthy microbiota is resistant to colonization with C. difficile. Dysbiosis, often caused by antimicrobial exposure, enables C. difficile spores to germinate and produce toxin, causing symptoms that can range from mild diarrhoea to fulminant colitis and death. This Review describes changes in epidemiology and effects on diagnosis, discusses recent breakthroughs in the understanding of pathogenesis and antibiotic resistance and explores the role of microbiota dysbiosis in CDI and novel microbiota therapies in CDI treatment.