Systemic Inflammatory Responses in Ulcerative Colitis Patients and Clostridium difficile Infection
Finding differences in systemic inflammatory response in ulcerative colitis (UC), UC with Clostridium difficile infection (CDI), and CDI could lead to a better ability to differentiate between UC with symptomatic CDI and UC with C. difficile colonization, and could identify specific inflammatory pathways for UC or CDI, which could be therapeutic targets.
We prospectively collected sera from symptomatic UC patients whose stools were tested for toxigenic C. difficile, and from CDI patients who did not have UC (CDI-noUC). The UC patients with positive tests (UC-CDI) were further categorized into responders to CDI treatment (UC-CDI-R) and non-responders (UC-CDI-NR). We compared serum inflammatory mediators among groups using unadjusted and adjusted multivariable statistics.
We included 117 UC [27 UC-CDI, 90 UC without CDI (UC-noCDI)] and 16 CDI-noUC patients. Principal component analysis (PCA) did not reveal significant differences either between UC-CDI and UC-noCDI groups, or between UC-CDI-R and UC-CDI-NR groups. In contrast, the PCA showed significant separation between the UC and CDI-noUC groups (P = 0.002). In these two groups, hepatocyte growth factor (HGF) and chemokine (C-C motif) ligand 2 (CCL2) levels were significantly lower and IL-23 levels were higher in UC patients in multivariable analyses. The model to distinguish UC from CDI including IL-23, HGF, CCL2, age, gender, and HGB had an AuROC of 0.93.
Inflammatory profiles could not distinguish UC-CDI from UC-noCDI, and UC-CDI-R from UC-CDI-NR. However, the UC and CDI-noUC groups were significantly different. Future work should examine whether therapeutic agents inhibiting IL-23 or stimulating HGF can treat UC.
KeywordsUlcerative colitis Clostridium difficile Cytokine Chemokine Growth factor Inflammatory biomarker
PDRH and KR were involved in study concept and design; JL, LJ, AR, and EB acquired data; JL, KR, and PDRH analyzed and interpreted the data; JL and KR drafted the manuscript; RWS, SMG, AKW, AR, and PDRH critically revised the manuscript for important intellectual content; PDRH was involved in study supervision.
This work was supported by the following grants. JL: Anandamahidol Foundation, Thailand. KR: the Claude D. Pepper Older Americans Independence Center [Grant Number AG-024824] and the Michigan Institute for Clinical and Health Research [Grant Number 2UL1TR000433]. PDRH: NIH R01 DK109032, R01 GM097117, and R21 AI122098. AKW: a Career Development Award (CDA 11-217) from the United States (U.S.) Department of Veterans Affairs Health Services Research and Development Service. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conflict of interest
All authors report no conflicts.
- 15.vegan: Community ecology package (2018). Available at https://CRAN.R-project.org/package=vegan.