title: Recent insights into Clostridium difficile pathogenesis.
abstract: OBJECTIVE
  Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in the healthcare setting. An emerging consensus suggests that CDI is caused by pathogenic toxin production, gut microbial dysbiosis and altered host inflammatory responses. The aim of this review is to summarize and highlight recent advances focused on CDI pathogenic mechanisms.
  
  
  RESULTS
  Potential paradigm shifts relating to the mechanisms of toxin action and inhibition have recently been reported, with new insights into spore germination and surface protein function also gaining traction. Multiomic analysis of microbiome dysbiosis has identified important CDI-associated microbial community shifts that may form the basis of future targeted bacteriotherapy, and functional metabolite biomarkers that require further characterization. Classical innate and adaptive immunity against CDI is rapidly being delineated, with novel innate S-nitrosylation signals also being identified.
  
  
  CONCLUSIONS
  Studies in patients and animal disease models are shedding new light on the critical roles of the microbiota, metabolome and host responses in primary and recurrent CDI. An improved understanding of the CDI disease pathogenesis will provide the basis for developing new therapies for treating disease and preventing recurrence.
authors: Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0435, USA.
authors: Alex G
authors: AG
authors: Peniche
authors: Tor C
authors: TC
authors: Savidge
authors: Sara M
authors: SM
authors: Dann
mesh_terms: D000818:Animals; D016360:Clostridioides difficile / Q000472:pathogenicity*; D003015:Clostridium Infections / Q000276:immunology / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D064307:Microbiota