A short chain fatty acid–centric view of Clostridioides difficile pathogenesis |
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Authors: | Anna L Gregory Daniel A Pensinger Andrew J Hryckowian |
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Institution: | 1. Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America;2. Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America;3. Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Geisel School of Medicine at Dartmouth, UNITED STATES |
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Abstract: | Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile–microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens. |
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