Abstract
Clostridium difficile-associated diarrhoea (CDAD) is caused by C. difficile toxins A and B and represents a serious emerging health problem. Yet, its progression and functional consequences are unclear. We hypothesised that C. difficile can drive major measurable metabolic changes in the gut microbiota and that a relationship with the production or absence of toxins may be established. We tested this hypothesis by performing metabolic profiling on the gut microbiota of patients with C. difficile that produced (n=6) or did not produce (n=4) toxins and on non-colonised control patients (n=6), all of whom were experiencing diarrhoea. We report a statistically significant separation (P-value <0.05) among the three groups, regardless of patient characteristics, duration of the disease, antibiotic therapy and medical history. This classification is associated with differences in the production of distinct molecules with presumptive global importance in the gut environment, disease progression and inflammation. Moreover, although severe impaired metabolite production and biological deficits were associated with the carriage of C. difficile that did not produce toxins, only previously unrecognised selective features, namely, choline- and acetylputrescine-deficient gut environments, characterised the carriage of toxin-producing C. difficile. Additional results showed that the changes induced by C. difficile become marked at the highest level of the functional hierarchy, namely the metabolic activity exemplified by the gut microbial metabolome regardless of heterogeneities that commonly appear below the functional level (gut bacterial composition). We discuss possible explanations for this effect and suggest that the changes imposed by CDAD are much more defined and predictable than previously thought.
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Acknowledgements
The present investigation was funded by the Spanish Ministry of Economy and Competitiveness and the Federal Ministry of Education and Research (BMBF) within the ERA NET PathoGenoMics2 program, grant number 0315441A. This work was further funded by grants BFU2008-04501-E, SAF2009-13032-C02-01, SAF2012-31187, CSD2007-00005 and BIO2011-25012 from the Spanish Ministry of Economy and Competitiveness, PrometeoII/2'14/065 from Generalitat Valenciana (Spain) and AGL2006-11697/ALI. We gratefully acknowledge the financial support provided by the European Regional Development Fund (ERDF). We thank Rafael Bargiela for his excellent support in relation to the preparation of Figure 3.
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Rojo, D., Gosalbes, M., Ferrari, R. et al. Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses. ISME J 9, 2206–2220 (2015). https://doi.org/10.1038/ismej.2015.32
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DOI: https://doi.org/10.1038/ismej.2015.32
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