| Summary: | <i>Clostridioides difficile</i> is an anaerobic Gram-positive and spore-forming bacterium. The majority of <i>C. difficile</i> strains produce two toxins, A and B, associated with the development of acute diarrhea and/or colitis. In this review, two situations are distinguished: <i>C. difficile</i> infection (CDI) and asymptomatic colonization (AC). The main objective of this review is to explore the available data related to the link between the gut microbiota and the development of CDI. The secondary aim is to provide more information on why some people colonized with toxigenic <i>C. difficile</i> develop an infection while others show no signs of disease. Several factors, such as the use of antibiotics and proton pump inhibitors, hospitalization, and age, predispose individuals to <i>C. difficile</i> colonization and/or <i>C. difficile</i> infection. The gut microbiota of people with AC showed decreased abundances of <i>Prevotella</i>, <i>Alistipes</i>, <i>Bacteroides</i>, <i>Bifidobacterium</i>, <i>Dorea</i>, <i>Coprococcus</i>, and <i>Roseburia</i>. The gut microbiota of people suffering from CDI showed reductions in the abundances of <i>Lachnospiraceae</i>, <i>Ruminococcaceae</i>, <i>Blautia</i> spp., <i>Prevotella</i> spp., <i>Dialister</i> spp., <i>Bifidobacterium</i> spp., <i>Roseburia</i> spp., <i>Anaerostipes</i> spp., <i>Faecalibacterium</i> spp. and <i>Coprococcus</i> spp., in comparison with healthy people. Furthermore, increases in the abundances of <i>Enterococcaceae</i> and <i>Enterococcus</i> were associated with <i>C. difficile</i> infection.
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