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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Main Authors: Tereena Lucas, Brent Brown
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Hygiene and Environmental Health Advances
Subjects:
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.
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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