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<p>High serum cholesterol levels are among the key risk factors for atherosclerosis cardiovascular disease. The utilization of probiotics to lower cholesterol is a relatively safe and efficient therapy, and the bile salt hydrolase gene serves a key function in this process. We aim to identify novel bile salt hydrolase genes from the wild western black crested gibbon (<i>Nomascus concolor</i>) faecal metagenome. Additionally, we intend to develop a new generation of probiotics with cholesterol-lowering properties. Our study amplified and heterologously expressed novel bile salt hydrolases from the faecal metagenome of western black crested gibbons and investigated their enzymatic properties. The recombinant probiotic was constructed using <i>Escherichia coli</i> Nissle 1917 (EcN), and its physiological characteristics and cholesterol-lowering ability were evaluated. We screened uncharacterized bile salt hydrolase genes (<i>NCbsh3</i> and <i>NCbsh5</i>) from <i>Eubacterium</i> and <i>Roseburia</i>. NCbsh3 exhibited broad pH adaptability and stability; its optimal pH range was 4–7, and the relative enzyme activity was maintained at 80% after 60&#xa0;min at pH 3–9. The recombinant probiotic EcN/NCbsh3 was constructed, and its bile salt tolerance and cholesterol-lowering ability significantly increased (<i>P</i> &lt; 0.05). These results indicated that NCbsh3 may adapt to the complex pH environment of the intestine and that the <i>NCbsh3</i> gene is expected to increase the colonization capacity of the EcN strain in the gastrointestinal tract and reduce host serum cholesterol levels. EcN/NCbsh3 has favourable application potential and may contribute positively to the treatment of diseases caused by bile acid metabolism disorders.</p>

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A Novel Broad pH-Adaptive Bile Salt Hydrolase from Nomascus concolor Fecal Microbial Metagenome Facilitates the Cholesterol-Lowering Ability of Escherichia coli Nissle 1917

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Yilin Wang,
  • Yanting Li,
  • Jianing Fang,
  • Zunxi Huang,
  • Chengbo Zhang,
  • Bo Xu

摘要

High serum cholesterol levels are among the key risk factors for atherosclerosis cardiovascular disease. The utilization of probiotics to lower cholesterol is a relatively safe and efficient therapy, and the bile salt hydrolase gene serves a key function in this process. We aim to identify novel bile salt hydrolase genes from the wild western black crested gibbon (Nomascus concolor) faecal metagenome. Additionally, we intend to develop a new generation of probiotics with cholesterol-lowering properties. Our study amplified and heterologously expressed novel bile salt hydrolases from the faecal metagenome of western black crested gibbons and investigated their enzymatic properties. The recombinant probiotic was constructed using Escherichia coli Nissle 1917 (EcN), and its physiological characteristics and cholesterol-lowering ability were evaluated. We screened uncharacterized bile salt hydrolase genes (NCbsh3 and NCbsh5) from Eubacterium and Roseburia. NCbsh3 exhibited broad pH adaptability and stability; its optimal pH range was 4–7, and the relative enzyme activity was maintained at 80% after 60 min at pH 3–9. The recombinant probiotic EcN/NCbsh3 was constructed, and its bile salt tolerance and cholesterol-lowering ability significantly increased (P < 0.05). These results indicated that NCbsh3 may adapt to the complex pH environment of the intestine and that the NCbsh3 gene is expected to increase the colonization capacity of the EcN strain in the gastrointestinal tract and reduce host serum cholesterol levels. EcN/NCbsh3 has favourable application potential and may contribute positively to the treatment of diseases caused by bile acid metabolism disorders.