| Summary: | <i>Clostridioides difficile</i> is an anaerobic spore-forming Gram-positive bacterium. <i>C. difficile</i> carriage and 16S rDNA profiling were studied in three clinical groups at three different sampling times: inflammatory bowel disease (IBD) patients, <i>C. difficile</i> infection (CDI) patients and healthcare workers (HCWs). Diversity analysis was realized in the three clinical groups, the positive and negative <i>C. difficile</i> carriage groups and the three analysis periods. Concerning the three clinical groups, β-diversity tests showed significant differences between them, especially between the HCW group and IBD group and between IBD patients and CDI patients. The Simpson index (evenness) showed a significant difference between two clinical groups (HCWs and IBD). Several genera were significantly different in the IBD patient group (<i>Sutterella</i>, <i>Agathobacter</i>) and in the CDI patient group (<i>Enterococcus</i>, <i>Clostridioides</i>). Concerning the positive and negative <i>C. difficile</i> carriage groups, β-diversity tests showed significant differences. Shannon, Simpson and InvSimpson indexes showed significant differences between the two groups. Several genera had significantly different relative prevalences in the negative group (<i>Agathobacter</i>, <i>Sutterella</i>, <i>Anaerostipes</i>, <i>Oscillospira</i>) and the positive group (<i>Enterococcus</i>, <i>Enterobacteriaceae</i>_ge and <i>Enterobacterales</i>_ge). A microbiota footprint was detected in <i>C. difficile</i>-positive carriers. More experiments are needed to test this microbiota footprint to see its impact on <i>C. difficile</i> infection.
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