Fernandez-Cotarelo, Maria-JoseJackson-Akers, Jasmine Y.Nagy-Agren, Stephanie E.Warren, Cirle A.2023-10-232023-10-232023-10-17European Journal of Medical Research. 2023 Oct 17;28(1):439http://hdl.handle.net/10919/116524Purpose: Clostridioides difficile infection (CDI) is the leading cause of antibiotic-related diarrhea and healthcare-associated infections, affecting in particular elderly patients and their global health. This review updates the understanding of this infection, with focus on cognitive impairment and frailty as both risk factors and consequence of CDI, summarizing recent knowledge and potential mechanisms to this interplay. Methods: A literature search was conducted including terms that would incorporate cognitive and functional impairment, aging, quality of life, morbidity and mortality with CDI, microbiome and the gut–brain axis. Results: Advanced age remains a critical risk for severe disease, recurrence, and mortality in CDI. Observational and quality of life studies show evidence of functional loss in older people after acute CDI. In turn, frailty and cognitive impairment are independent predictors of death following CDI. CDI has long-term impact in the elderly, leading to increased risk of readmissions and mortality even months after the acute event. Immune senescence and the aging microbiota are key in susceptibility to CDI, with factors including inflammation and exposure to luminal microbial products playing a role in the gut–brain axis. Conclusions: Frailty and poor health status are risk factors for CDI in the elderly. CDI affects quality of life, cognition and functionality, contributing to a decline in patient health over time and leading to early and late mortality. Narrative synthesis of the evidence suggests a framework for viewing the cycle of functional and cognitive decline in the elderly with CDI, impacting the gut–brain and gut–muscle axes.application/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereed2023-10-22BioMed Central Ltd., part of Springer Naturehttps://doi.org/10.1186/s40001-023-01432-9