ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microorganisms in Vertebrate Digestive Systems

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1599931

This article is part of the Research TopicLactic Acid Bacteria and their Bioactive Compounds: Key Regulators of Gut Microbiota and Immune FunctionView all 13 articles

Lactobacillus paragasseri HM018 Derived from Breast Milk Ameliorates Hyperlipidemia in High-Cholesterol Rats by Modulating Bile Acid Metabolism

Provisionally accepted
Chunyu  YaoChunyu Yao1,2Xianping  LiXianping Li1Mi  TangMi Tang1,3Lu  LiuLu Liu1Xiaoqian  CaiXiaoqian Cai1,4Xueping  YuanXueping Yuan1,2Jufeng  HuJufeng Hu1Junying  ZhaoJunying Zhao1Weicang  QiaoWeicang Qiao1Yue  ZhangYue Zhang2*Lijun  ChenLijun Chen1,2,3*
  • 1National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co., Ltd., Beijing, China
  • 2School of Biological Engineering, Dalian Polytechnic University, Dalian, China
  • 3Key Laboratory of Dairy Science, College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China
  • 4College of Life Sciences, Inner Mongolia University, Hohhot, China

The final, formatted version of the article will be published soon.

Hyperlipidemia, a prevalent metabolic disorder with rising global incidence, has become a major public health concern. Probiotics allow for a mild intervention strategy for hyperlipidemia management that has garnered increasing attention. In this study, we investigated the therapeutic effects and underlying mechanisms of Lactobacillus paragasseri HM018 in hypercholesterolemic rats. We established three dosage groups (2.5×10⁸, 5×10⁸, and 1.5×10⁹ CFU/rat), demonstrating that HM018 significantly reduced high-fat diet-induced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, while ameliorating gut microbiota dysbiosis and decreasing the Firmicutes/Bacteroidetes ratio. Our transcriptomic analysis revealed that HM018 markedly upregulated Apoa1 expression both in the ileum and liver, while enhancing Abcg5/Abcg8 gene expression to promote β-sitosterol efflux. Concurrently, hepatic Cocs2/3 and Cish gene expression was downregulated, attenuating their inhibitory effects on hormonal and glucagon signaling, thereby improving glucose and lipid metabolism. Metabolomic profiling further indicated that HM018 significantly altered bile acid composition by modulating gut microbiota-mediated bile acid metabolism. In conclusion, Lactobacillus paracasei HM018 could ameliorate hyperlipidemia through multiple pathways, including gut microbiota modulation, hepatic lipid/glucose/bile acid metabolism improvement, and intestinal cholesterol efflux gene expression enhancement.

Keywords: Hyperlipidemia, Breast milk-derived probiotics, Lactobacillus paragasseri, Gut Microbiota, Bile acid metabolism, Cholesterol efflux

Received: 25 Mar 2025; Accepted: 12 May 2025.

Copyright: © 2025 Yao, Li, Tang, Liu, Cai, Yuan, Hu, Zhao, Qiao, Zhang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yue Zhang, School of Biological Engineering, Dalian Polytechnic University, Dalian, China
Lijun Chen, National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co., Ltd., Beijing, China

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