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

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  • 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
  • Huijue Jia
  • Shilong Zhong
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.
OriginalsprogEngelsk
Artikelnummer106960
TidsskriftiScience
Vol/bind26
Udgave nummer6
Antal sider22
ISSN2589-0042
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was funded by the National Natural Science Foundation of China (No. 81872934, 81673514 [Principle investigator: Shilong Zhong]), Science and Technology Program of Guangzhou (No. 2023B03J1251 [Principle investigator: Shilong Zhong]), the Key Area Research and Development Program of Guangdong Province, China (No. 2019B020229003 [Principle investigator: Shilong Zhong]), Science and Technology Development Projects of Guangdong Province (2019A050510025 [Principle investigator: Yong Li]), Excellent Young Talent Program of GDPH (KY012021187 [Principle investigator: Xiao Xiao]). The authors are very grateful to colleagues at BGI-Shenzhen and China National Genebank (CNGB), Shenzhen, for sample collection, DNA extraction, library construction, sequencing, and discussions. S.Z. was the principal investigator of this study and designed the study. Z.J. performed the data analysis and drafted the manuscript. Q.Z. and Y.Z. performed the experiment and drafted the manuscript. Q.W. performed the experiment and revised the manuscript. M.Q. performed data analysis and revised the manuscript. D.H. X.L. X.T. J.Z. Zhu Jie, W.L. X.X. S.C. Y.W. G.G. and Shufen Zheng were assisted in data acquisition and experiment. Y.L. Weihua Lai, H.Y. J.W. L.X. J.C. and T.Z. assisted in data curation and revised the manuscript. K.K. and H.J. provided resources and critically revised the manuscript. All authors reviewed and approved the final manuscript. The authors declare no competing financial interest. We support inclusive, diverse, and equitable conduct of research.

Funding Information:
This study was funded by the National Natural Science Foundation of China (No. 81872934 , 81673514 [Principle investigator: Shilong Zhong]), Science and Technology Program of Guangzhou (No. 2023B03J1251 [Principle investigator: Shilong Zhong]), the Key Area Research and Development Program of Guangdong Province, China (No. 2019B020229003 [Principle investigator: Shilong Zhong]), Science and Technology Development Projects of Guangdong Province ( 2019A050510025 [Principle investigator: Yong Li]), Excellent Young Talent Program of GDPH ( KY012021187 [Principle investigator: Xiao Xiao]). The authors are very grateful to colleagues at BGI-Shenzhen and China National Genebank (CNGB), Shenzhen, for sample collection, DNA extraction, library construction, sequencing, and discussions.

Publisher Copyright:
© 2023

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