Strain-level screening of human gut microbes identifies Blautia producta as a new anti-hyperlipidemic probiotic

ABSTRACT

Compelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, Blautia producta exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of Bl. Producta. In vivo experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on Bl. producta and its metabolite.

KEYWORDS:

• Functional strain screening
• gut microbiota
• hyperlipidemia
• Blautia producta
• 12-methylmyristic acid (12-MMA)
• G protein-coupled receptor 120 (GPR120)

Authors’ contributions

CW and BZ conceived the project, designed the experiments. WX and JY performed most of the experiments with the help of YY, ZL, YZ, FZ, YX and QW. CW and WX prepared figures and wrote the manuscript. BZ and ZL provided the gut bacteria samples. All authors discussed the manuscript, commented on the project, and contributed to manuscript preparation.

Disclosure statement

WX, ZL, YZ, QW, and BZ are employees of Beijing QuantiHealth Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

The sequencing raw data and genome sequences in the present study have been deposited in the National Center for Biotechnology Information (NCBI) database, and the project numbers are PRJNA771420 (https://www.ncbi.nlm.nih.gov//bioproject/PRJNA771420), PRJNA771488 (https://www.ncbi.nlm.nih.gov//bioproject/PRJNA771488) and PRJNA771491 (https://www.ncbi.nlm.nih.gov//bioproject/PRJNA771491). Other data relevant to the study are included in the article or uploaded as supplementary files.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2228045

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported financially by the National Natural Science Foundation of China (Grant 81973217 to CW), and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant 2018RC350014 to CW).