Abstract
Hyperlipidemia is a leading global health challenge, limited by the safety liabilities of current pharmacotherapies. Here, we isolated a novel Limosilactobacillus reuteri strain, MacFasB02, from fecal samples of cynomolgus monkeys tolerant to chronic high-fat diet (HFD). This study aimed to systematically evaluate its probiotic properties and therapeutic potential against hyperlipidemia. In vitro, MacFasB02 exhibited robust growth, acid production, and tolerance to acidic and bile environments. In HFD-fed mice, 13-week MacFasB02 administration reduced weight gain, serum triglycerides, low-density lipoprotein cholesterol and total cholesterol, while ameliorating hepatic steatosis and inflammation, as well as restoring intestinal barrier integrity by enhanced villus architecture, goblet cell function, and tight junction proteins expression. Metagenomic analysis revealed gut microbiota remodeling. Transcriptomic profiling coupled with in vivo validation demonstrated upregulation of Apoa1 and Pltp in cholesterol metabolism. Untargeted metabolomics integrated with whole-genome sequencing and supernatant metabolite profiling identified adenosine as a key MacFasB02-derived metabolite in purine metabolism. Consistently, In vitro experiments showed that adenosine reduced lipid accumulation and inflammation in hepatocytes by regulating Apoa1 and Pltp to modulate cholesterol metabolism. Collectively, MacFasB02 exerts dual lipid-lowering and anti-inflammatory effects probably via adenosine-mediated modulation of cholesterol metabolism, promising potential as a live biopharmaceutical agent for hyperlipidemia.
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Data availability
The multi-omics data generated in this study have been deposited in the OMIX database (https://ngdc.cncb.ac.cn/omix) and GSA database (https://ngdc.cncb.ac.cn/gsub) at the China National Center for Bioinformation. OMIX013581: Non-targeted metabolomics of MacFasB02 culture medium Supernatant. Access link: https://ngdc.cncb.ac.cn/omix/release/OMIX013581. OMIX013583: Non-targeted metabolomics of mouse cecal contents. Access link: https://ngdc.cncb.ac.cn/omix/release/OMIX013583. CRA034905: Whole-genome sequencingof MacFasB02. Access link: https://ngdc.cncb.ac.cn/gsa/s/qwRF2z5T. CRA034902: Transcriptome sequencing of mouse liver samples. Access link: https://ngdc.cncb.ac.cn/gsa/s/XjRXx8S. CRA035096: Metagenomic Sequencing of mouse fecal samples. Access link: https://ngdc.cncb.ac.cn/gsa/s/22XFWxI1. CRA035456: Sanger sequencing identification of MacFasB02. Access link: https://ngdc.cncb.ac.cn/gsa/s/NBo8148Z.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 82471097 and 82200966), the Guangdong Key Laboratory of Nonhuman Primate Research (2020B121201006), Guangdong Provincial Science and Technology Leading Talent Project (210183503006). GDAS' Project of Science and Technology Development (2024GDASZH-2024010101).
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Y.J., H.J.A., J.H.R., and J.H.C. conceived and designed the study. Y.J., H.J.A., T.T.Z., J.M.G., X.L.Z., B.H.L., Y.Y.L., and X.J.Z. performed the experiments. Y.J., H.J.A., and J.J.L. analyzed the data. Y.J. wrote the original draft of the manuscript. Y.J., J.H.R., and J.H.C. contributed to writing, reviewing, and editing the manuscript. J.H.R. and J.H.C. supervised the research. J.H.R. and J.H.C. administered the project.
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Jin, Y., An, HJ., Zheng, TT. et al. Adenosine from high-fat-diet-tolerant monkey-derived Limsolactobacillus reuteri MacFasB02 modulates cholesterol metabolism to alleviate hyperlipidemia and inflammation. npj Sci Food (2026). https://doi.org/10.1038/s41538-026-00765-z
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DOI: https://doi.org/10.1038/s41538-026-00765-z
