Gene Expression Dysregulation in Whole Blood of Patients with Clostridioides difficile Infection

<i>Clostridioides difficile</i> (<i>C. difficile</i>) is a global threat and has significant implications for individuals and health care systems. Little is known about host molecular mechanisms and transcriptional changes in peripheral immune cells. This is the first gene expression study in whole blood from patients with <i>C. difficile</i> infection. We took blood and stool samples from patients with toxigenic <i>C. difficile</i> infection (CDI), non-toxigenic <i>C. difficile</i> infection (GDH), inflammatory bowel disease (IBD), diarrhea from other causes (DC), and healthy controls (HC). We performed transcriptome-wide RNA profiling on peripheral blood to identify diarrhea common and CDI unique gene sets. Diarrhea groups upregulated innate immune responses with neutrophils at the epicenter. The common signature associated with diarrhea was non-specific and shared by various other inflammatory conditions. CDI had a unique 45 gene set reflecting the downregulation of humoral and T cell memory functions. Dysregulation of immunometabolic genes was also abundant and linked to immune cell fate during differentiation. Whole transcriptome analysis of white cells in blood from patients with toxigenic <i>C. difficile</i> infection showed that there is an impairment of adaptive immunity and immunometabolism.