Fecal S100 calcium-binding protein B as a marker for disease severity in patients with Clostridioides difficile infection

Clostridioides difficile infection (CDI) is an urgent threat in the United States (US). The severity of the disease is strongly correlated with intestinal inflammation. Biomarkers of intestinal inflammation can be detected in fecal specimens. The aim of this study was to investigate whether fecal S100 calcium-binding protein B (S100B) is associated with poor CDI outcomes. Fecal samples from patients diagnosed with CDI were collected from April 2021 to February 2022. Levels of S100B and other known biomarkers for intestinal inflammation (myeloperoxidase-MPO, lipocalin-2-Lcn2, calprotectin-S100A8/A9, IL-6, and brain-derived neurotrophic factor-BDNF) were measured in fecal specimens by ELISA. C. difficile isolates from matched fecal specimens were tested for the binary toxin genes ( cdtA/cdtB ) by qPCR. The majority of patients were female (59.06%, 88/149), and a mean age of 61.4 years (range, 21 to 96 years). In addition, 42.28% (63/149) of the patients exhibited severe disease, 29.53% (44/149) were recurrent CDI cases, 59% (88/149) were infected with a binary-positive strain, and 19.46% (29/149) died post-infection. Fecal levels of S100B, but not IL-6, MPO, Lcn2, S100A8/A9, or BDNF, were significantly increased in severe CDI cases. Fecal S100B was associated with severe disease (AUC = 0.6253, p = 0.0091) but not post-CDI mortality or recurrent disease status. Higher fecal S100B levels were more likely in patients with severe CDI. All biomarkers combined together (S100B, IL-6, MPO, Lcn2, S100A8/A9, and BDNF) were associated with severe disease, recurrence and mortality post-CDI. Our findings indicate that higher fecal S100B levels are associated with severe CDI.