Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency

Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy. Atherosclerosis: A role for gut microbes Transplanting fecal matter into the guts of mice used as a model of atherosclerosis suggests a role for gut microbes in causing, preventing and potentially treating this serious condition. Atherosclerosis is the build-up of fatty deposits in artery walls, often called hardening of the arteries. Eun Sil Kim and colleagues at Asan Medical Center, University of Ulsan College of Medicine in Seoul, South Korea, analyzed the gut microbes of mice that had been genetically altered to develop atherosclerosis. The gut microbial populations of the mice with atherosclerosis were significantly different from those of normal mice used as controls. Fecal transplantation from control mice into atherosclerotic mice halted the progression of atherosclerosis, with transplantation in the opposite direction promoting atherosclerosis. Macrophage cells of the immune system seem to be involved in the protective effect of beneficial gut microbes.

Automated summary

This study reveals the association between CTRP9 gene deficiency and gut microbiota distribution in patients with atherosclerosis, confirms the influence of gut microbiota on the progression of atherosclerosis, and suggests restoring gut microbial homeostasis as a potential therapeutic strategy.