Expansion of a versatile pathogen: Clostridioides difficile
Clostridioides difficile is a gram positive and spore forming bacterium responsible for significant global morbidity and mortality. There is increasing incidence of C. difficile disease that constitutes a deviation from the traditionally understood toxin-mediated colonic disease. Comprehensive liter...
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Elsevier
2024-12-01
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| Series: | Hygiene and Environmental Health Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773049224000217 |
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| author | Tereena Lucas Brent Brown |
| author_facet | Tereena Lucas Brent Brown |
| author_sort | Tereena Lucas |
| collection | DOAJ |
| description | Clostridioides difficile is a gram positive and spore forming bacterium responsible for significant global morbidity and mortality. There is increasing incidence of C. difficile disease that constitutes a deviation from the traditionally understood toxin-mediated colonic disease. Comprehensive literature review has determined a conservative increase of over 600 cases of C. difficile extra–intestinal and small–intestinal disease detailed in >200 papers over the past 20 years. Chronic colonization with increased intestinal permeability that permits the translocation of toxins and metabolites may partially explain this expanded disease manifestation. Currently there is little evidence in support of a role for toxins however, and greater evidence to support the role of metabolites in extra-intestinal disease pathogenesis. Specifically, increased levels of p-cresol, p-cresyl sulfate, indoxyl sulfate and ammonia are associated with C. difficile colonization. One important health consideration involves ongoing biotransformation of such metabolites, together with the overall metabolic load from all endogenous and exogenous sources, that can result in glutathione depletion. Chronic glutathione depletion in turn increases oxidative stress and is correlated with neurological compromise across all age groups, and a host of other conditions. Key factors supporting chronic colonization with C. difficile in susceptible hosts include widespread and indiscriminate use of antimicrobials, pharmaceuticals, pesticides, intensive agricultural practices, diet, food additives, and gastrointestinal disturbances. Appreciation of the role of the exposome in C. difficile disease expansion will further emphasize the importance of decreasing environmental contamination, antimicrobial resistance, inter-species transmission, and individual toxic metabolite burdens. |
| format | Article |
| id | doaj-art-ed8ad4ff7c654f1abceeffa83b8a4e9d |
| institution | OA Journals |
| issn | 2773-0492 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Hygiene and Environmental Health Advances |
| spelling | doaj-art-ed8ad4ff7c654f1abceeffa83b8a4e9d2025-08-20T02:21:07ZengElsevierHygiene and Environmental Health Advances2773-04922024-12-011210010810.1016/j.heha.2024.100108Expansion of a versatile pathogen: Clostridioides difficileTereena Lucas0Brent Brown1Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Scotland, UK; Corresponding author at: School of Population Health, Health Sciences, Curtin University, Perth, Western Australia.Academic Researcher, London, NW7 4AU, UKClostridioides difficile is a gram positive and spore forming bacterium responsible for significant global morbidity and mortality. There is increasing incidence of C. difficile disease that constitutes a deviation from the traditionally understood toxin-mediated colonic disease. Comprehensive literature review has determined a conservative increase of over 600 cases of C. difficile extra–intestinal and small–intestinal disease detailed in >200 papers over the past 20 years. Chronic colonization with increased intestinal permeability that permits the translocation of toxins and metabolites may partially explain this expanded disease manifestation. Currently there is little evidence in support of a role for toxins however, and greater evidence to support the role of metabolites in extra-intestinal disease pathogenesis. Specifically, increased levels of p-cresol, p-cresyl sulfate, indoxyl sulfate and ammonia are associated with C. difficile colonization. One important health consideration involves ongoing biotransformation of such metabolites, together with the overall metabolic load from all endogenous and exogenous sources, that can result in glutathione depletion. Chronic glutathione depletion in turn increases oxidative stress and is correlated with neurological compromise across all age groups, and a host of other conditions. Key factors supporting chronic colonization with C. difficile in susceptible hosts include widespread and indiscriminate use of antimicrobials, pharmaceuticals, pesticides, intensive agricultural practices, diet, food additives, and gastrointestinal disturbances. Appreciation of the role of the exposome in C. difficile disease expansion will further emphasize the importance of decreasing environmental contamination, antimicrobial resistance, inter-species transmission, and individual toxic metabolite burdens.http://www.sciencedirect.com/science/article/pii/S2773049224000217Clostridioides difficileExposomeCommunity-acquiredMetabolitesExtra-intestinal diseaseOne Health |
| spellingShingle | Tereena Lucas Brent Brown Expansion of a versatile pathogen: Clostridioides difficile Hygiene and Environmental Health Advances Clostridioides difficile Exposome Community-acquired Metabolites Extra-intestinal disease One Health |
| title | Expansion of a versatile pathogen: Clostridioides difficile |
| title_full | Expansion of a versatile pathogen: Clostridioides difficile |
| title_fullStr | Expansion of a versatile pathogen: Clostridioides difficile |
| title_full_unstemmed | Expansion of a versatile pathogen: Clostridioides difficile |
| title_short | Expansion of a versatile pathogen: Clostridioides difficile |
| title_sort | expansion of a versatile pathogen clostridioides difficile |
| topic | Clostridioides difficile Exposome Community-acquired Metabolites Extra-intestinal disease One Health |
| url | http://www.sciencedirect.com/science/article/pii/S2773049224000217 |
| work_keys_str_mv | AT tereenalucas expansionofaversatilepathogenclostridioidesdifficile AT brentbrown expansionofaversatilepathogenclostridioidesdifficile |