Statin treatment facilitates Campylobacter jejuni colonization in the gastrointestinal tract in mouse infection model

Abstract

Campylobacter jejuni causes human foodborne infectious disease worldwide. In C. jejuni-infection, bacterial adherence to and invasion of the host epithelial cells are suspected to be initial factors for virulence. This bacterium used host cellular cholesterol-rich domain, lipid raft, for bacterial internalization. Thus, cholesterol is considered a key factor in the C. jejuni-infection in vitro experiment model. Nevertheless, there is no experimental report that examines cholesterol participation in C. jejuni-infection in an experimental mouse model. Herein, cholesterol distribution on C. jejuni-infectible mice was analyzed. Plasma and stool cholesterol and cholesterol derived deoxycholic acid (DCA) levels in stool were lower in antibiotic-treated, C. jejuni-susceptible, mice (Abs-PBS) than in untreated controls (water-PBS), but were recovered by C. jejuni infection (Abs-CJ). In this infection, the expression level of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) was significantly upregulated in the liver. Interestingly, the administration of statin, an inhibitor of HMGCR, increased the colonization of C. jejuni with the reduction of DCA in the gastrointestinal tract. Hence, it was suggested that the upregulation of cholesterol biosynthesis was involved in the defense system for C. jejuni-infection, which facilitates cholesterol-derived DCA-mediated bacterial clearance. J. Med. Invest. 73 : 494-502, August, 2026