A consortium of three-bacteria isolated from human feces inhibits formation of atherosclerotic deposits and lowers lipid levels in a mouse model

Zhuye Jie; Qian Zhu; Yuanqiang Zou; Qili Wu; Min Qin; Dongdong He; Xiaoqian Lin; Xin Tong; Jiahao Zhang; Zhu Jie; Wenwei Luo; Xiao Xiao; Shiyu Chen; Yonglin Wu; Gongjie Guo; Shufen Zheng; Yong Li; Weihua Lai; Huanming Yang; Jian Wang; Liang Xiao; Jiyan Chen; Tao Zhang; Karsten Kristiansen; Huijue Jia; Shilong Zhong

doi:10.1016/j.isci.2023.106960

A consortium of three-bacteria isolated from human feces inhibits formation of atherosclerotic deposits and lowers lipid levels in a mouse model

iScience. 2023 May 23;26(6):106960. doi: 10.1016/j.isci.2023.106960. eCollection 2023 Jun 16.

Authors

Zhuye Jie^{1

2

3}, Qian Zhu^{4

5

6}, Yuanqiang Zou^{1

3

7

8}, Qili Wu^{4

5

6}, Min Qin^{4

5

6}, Dongdong He¹, Xiaoqian Lin¹, Xin Tong¹, Jiahao Zhang¹, Zhu Jie¹, Wenwei Luo^{4

5}, Xiao Xiao^{4

5}, Shiyu Chen^{4

5}, Yonglin Wu^{4

5}, Gongjie Guo^{4

5

6}, Shufen Zheng^{4

5}, Yong Li⁹, Weihua Lai⁴, Huanming Yang^{1

10}, Jian Wang^{1

10}, Liang Xiao^{1

7

8}, Jiyan Chen⁵, Tao Zhang^{1

2

3}, Karsten Kristiansen^{1

3

7}, Huijue Jia^{1

2}, Shilong Zhong^{4

5

6}

Affiliations

¹ BGI-Shenzhen, Shenzhen, China.
² Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China.
³ Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark.
⁴ Department of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China.
⁵ Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China.
⁶ School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China.
⁷ Qingdao-Europe Advanced Institute for Life Sciences, BGI-Shenzhen, Qingdao 266555, China.
⁸ Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, China.
⁹ Department of Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China.
¹⁰ James D. Watson Institute of Genome Sciences, Hangzhou, China.

Abstract

By a survey of metagenome-wide association studies (MWAS), we found a robust depletion of Bacteroides cellulosilyticus, Faecalibacterium prausnitzii, and Roseburia intestinalis in individuals with atherosclerotic cardiovascular disease (ACVD). From an established collection of bacteria isolated from healthy Chinese individuals, we selected B. cellulosilyticus, R. intestinalis, and Faecalibacterium longum, a bacterium related to F. prausnitzii, and tested the effects of these bacteria in an Apoe^/- atherosclerosis mouse model. We show that administration of these three bacterial species to Apoe^-/- mice robustly improves cardiac function, reduces plasma lipid levels, and attenuates the formation of atherosclerotic plaques. Comprehensive analysis of gut microbiota, plasma metabolome, and liver transcriptome revealed that the beneficial effects are associated with a modulation of the gut microbiota linked to a 7α-dehydroxylation-lithocholic acid (LCA)-farnesoid X receptor (FXR) pathway. Our study provides insights into transcriptional and metabolic impact whereby specific bacteria may hold promises for prevention/treatment of ACVD.

Keywords: Bacteriology; Human metabolism; Microbial metabolism; Microbiology.