title: Evaluation of gastrointestinal leakage using serum (1→3)-β-D-glucan in a Clostridium difficile murine model.
abstract: 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 fluorescein isothiocyanate-dextran (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 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, S: erum 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 a therapeutic efficacy indicator.
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Asada
authors: A
authors: Leelahavanichkul
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand.
authors: Wimonrat
authors: W
authors: Panpetch
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand.
authors: Navaporn
authors: N
authors: Worasilchai
authors: Research Affairs, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand.
authors: Poorichaya
authors: P
authors: Somparn
authors: Division of Nephrology and Hypertension, Department of Medicine, Faculty of Medicine, Princess Chulabhorn College of Medical Sciences, Chulabhorn Royal Academy of Science (CRAS), Vipavadee road, Bangkok 10210, Thailand.
authors: Wiwat
authors: W
authors: Chancharoenthana
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand.
authors: Sumanee
authors: S
authors: Nilgate
authors: Department of Clinical Development, Associates of Cape Cod, Inc., 124 Bernard E. St. Jean Drive, East Falmouth, MA 02536, USA.
authors: Malcolm
authors: M
authors: Finkelman
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand.
authors: Ariya
authors: A
authors: Chindamporn
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand somying.T@chula.ac.th.
authors: Somying
authors: S
authors: Tumwasorn
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D054426:Chemokine CXCL2 / Q000097:blood; D016360:Clostridioides difficile / Q000302:isolation & purification; D003967:Diarrhea / Q000382:microbiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000097:blood / Q000382:microbiology / Q000503:physiopathology*; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D052201:Lacticaseibacillus rhamnosus; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010539:Permeability; D019936:Probiotics / Q000627:therapeutic use; D012372:ROC Curve; D047071:beta-Glucans / Q000097:blood*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D054426:Chemokine CXCL2; D047071:beta-Glucans
keywords: (1→3)-β-D-glucan; Clostridium difficile; gastrointestinal leakage; murine model