The study investigates the fecal microbiota of patients with recurrent Clostridium difficile-associated diarrhea (CDAD) using 16S rRNA-encoding gene sequence analysis. Patients with recurrent CDAD showed highly variable bacterial compositions and significantly decreased microbial diversity compared to control subjects and those with initial episodes. The findings suggest that preserving and restoring microbial diversity could be novel strategies for preventing and treating recurrent CDAD, which is often resistant to current therapies. The study highlights the importance of the gut microbiome in maintaining colonization resistance against C. difficile and provides evidence that decreased microbial diversity is associated with recurrent CDAD.The study investigates the fecal microbiota of patients with recurrent Clostridium difficile-associated diarrhea (CDAD) using 16S rRNA-encoding gene sequence analysis. Patients with recurrent CDAD showed highly variable bacterial compositions and significantly decreased microbial diversity compared to control subjects and those with initial episodes. The findings suggest that preserving and restoring microbial diversity could be novel strategies for preventing and treating recurrent CDAD, which is often resistant to current therapies. The study highlights the importance of the gut microbiome in maintaining colonization resistance against C. difficile and provides evidence that decreased microbial diversity is associated with recurrent CDAD.