We previously studied CDI in mice that develop obesity as a result of mutations in leptin signaling pathway.17 To avoid the confounding effects of genetic deletion on host physiology,18 in this study we used a well-defined mouse model of obesity where wildtype (WT) C57BL/6 mice were fed an obesogenic high-fat diet (HFD) before infection.19 Here, we show that compared to RD (regular chow diet)-fed mice, HFD-induced obese mice exhibit severe and protracted CDI-induced diarrhea, weight loss, and colonic damage. The gene discussed is LEP; the disease is obesity disorder.