Microbial Colonization of Germ‐Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury

BACKGROUND: The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. METHODS AND RESULTS: We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age‐, sex‐, and strain‐matched germ‐free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ‐free cohorts served as comparison groups. CONCLUSIONS: Germ‐free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.