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Background <p><i>Coptidis Rhizoma</i>, the rhizome of Coptis chinensis&#xa0;Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.</p> Methods <p>Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25&#xa0;mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and <i>Akkermansia</i> was studied for metabolic effects, analyzing plasma and fecal metabolomics.</p> Results <p>Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified <i>Akkermansia</i> as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced <i>Akkermansia</i> growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 ‘-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and <i>Akkermansia</i> amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.</p> Conclusion <p>Berberine, through <i>Akkermansia</i>, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with <i>Akkermansia</i> enhances its efficacy against hyperlipidemia.</p> Graphical Abstract <p></p>

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Berberine ameliorates high-fat diet-induced metabolic disorders through promoting gut Akkermansia and modulating bile acid metabolism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Wei-jian Hang,
  • Rui Yin,
  • Xi-wei Kang,
  • Lu He,
  • Xuan Cao,
  • Juan Chen

摘要

Background

Coptidis Rhizoma, the rhizome of Coptis chinensis Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.

Methods

Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25 mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and Akkermansia was studied for metabolic effects, analyzing plasma and fecal metabolomics.

Results

Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified Akkermansia as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced Akkermansia growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 ‘-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and Akkermansia amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.

Conclusion

Berberine, through Akkermansia, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with Akkermansia enhances its efficacy against hyperlipidemia.

Graphical Abstract