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The gut microbial ecosystem is a complex community of microorganisms that maintains intestinal homeostasis and provides colonization resistance against opportunistic pathogens [1]. Clostridioides difficile (formerly Clostridium difficile) is a Gram-positive, toxin-producing bacterium that exploits disruptions in this ecosystem, often caused by broad-spectrum antibiotics, to cause severe diarrhea and colitis [2]. As a therapeutic target, this system is addressed through two primary strategies: the direct elimination of the pathogen and the restoration of the protective microbial flora [3]. Traditional antibiotics like vancomycin and fidaxomicin target the bacterium's vital processes, while monoclonal antibodies like bezlotoxumab neutralize its toxins [4]. Emerging live biotherapeutic products, such as Rebyota and Vowst, aim to repair the gut microbial ecosystem itself to prevent recurrent infections [5].
Drugs targeting this system work through several distinct mechanisms: vancomycin inhibits bacterial cell wall synthesis, fidaxomicin inhibits bacterial RNA polymerase, and bezlotoxumab binds and neutralizes Clostridioides difficile Toxin B [4]. Additionally, live biotherapeutic products and fecal microbiota transplants restore the diversity of the gut microbial ecosystem, thereby re-establishing colonization resistance to suppress the overgrowth of C. difficile [5].
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