Intestinal Clostridioides difficile Can Cause Liver Injury through the Occurrence of Inflammation and Damage to Hepatocytes

Abstract

This study investigated if intestinal Clostridioides difficile (CD) causes liver injury. Four-week-old male C3H/HeN mice were treated with phosphate-buffered solution (control), CD, diethylnitrosamine (DEN) to induce liver injury with PBS (DEN+PBS), and DEN with CD (DEN+CD) for nine weeks. After sacrifice, livers and mesenteric lymph nodes (MLNs) were removed and bacterial translocation, transcriptomes, and proteins were analysed. CD was found in 20% of MLNs from the control and DEN+PBS groups, in 30% of MLNs from the CD group, and in 75% of MLNs from the DEN+CD groups, which had injured livers. Also, CD was detected in 50% of the livers in the DEN+CD group with CD-positive MLNs. Elevated IL-1β, HB-EGF, EGFR, TGF-α, PCNA, DES, HMGB1, and CRP expressions were observed in the CD and DEN+CD groups as compared to the control and DEN+PBS groups. Protein levels of IL-6 and HMGB1 were higher in the CD and DEN+CD groups than in the control and DEN+PBS groups. These results indicate that intestinal CD can initiate and aggravate liver injury, and the mechanism of pathogenesis for liver injury should be investigated in further studies.