Evaluation of gastrointestinal leakage using serum (1->3)-{beta}-D-glucan in a Clostridium difficile murine model

Gastrointestinal (GI) leakage in Clostridium difficile-associated diarrhea (CDAD) is well-known but is not routinely assessed in clinical practice. Serum (1->3)-β-D-glucan (BG), a fungal cell wall component used as a biomarker for invasive fungal disease, was tested in a CDAD mouse model with and without probiotics. Higher serum FITC-dextran and spontaneous gram negative bacteremia, GI leakage indicators, were frequently found in CDAD mice which died compared with those which survived. BG, serum macrophage inflammatory protein-2 and FITC-dextran but not quantitative blood bacterial count differentiated the clinical severity. Interestingly, a specific dose of Lactobacillus rhamnosus L34 attenuated CDAD and decreased serum BG and FITC-dextran, but not other parameters. BG also showed a higher area under the receiver operating characteristic curve (ROC) for 7 day mortality than FITC-dextran. Fifty-five percent of CDAD mice with BG ≥ 60 pg/ml (the human negative cut-off value for invasive fungal disease) at 1 day after C. difficile gavage died within 7 days. In conclusion, serum BG was elevated in mice with severe CDAD, an established model of GI leakage with a strong association with mortality rate. BG monitoring in patients with CDAD is of interest as both a potential prognostic tool and as a therapeutic efficacy indicator.

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