Abstract
Clostridium difficile infection (CDI) is intricately linked to the health of the gastrointestinal tract and its indigenous microbiota. In this study, we assessed whether fecal excretion of host DNA is associated with CDI development. Assuming that shedding of epithelial cell increases in the inflamed intestine, we used human DNA excretion as a marker of intestinal insult. Whole-genome shotgun sequencing was employed to quantify host DNA excretion and evaluate bacterial content in fecal samples collected from patients with incipient CDI, hospitalized controls, and healthy subjects. Human DNA excretion was significantly increased in patients admitted to the hospital for a gastrointestinal ailment, as well as prior to an episode of CDI. In multivariable analyses, human read abundance was independently associated with CDI development. Host DNA proportions were negatively correlated with intestinal microbiota diversity. Enterococcus and Escherichia were enriched in patients excreting high quantities of human DNA, while Ruminococcus and Odoribacter were depleted. These findings suggest that intestinal inflammation can occur prior to CDI development and may influence patient susceptibility to CDI. The quantification of human DNA in feces could serve as a simple and noninvasive approach to assess bowel inflammation and identify patients at risk of CDI.