Berberine improves drug-induced liver injury in mice by modulating gut microbiota

TU Dianji; ZHOU Jiyin

doi:10.16016/j.2097-0927.202508007

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Berberine improves drug-induced liver injury in mice by modulating gut microbiota

Basic Medicine | 更新时间：2025-12-25

- Berberine improves drug-induced liver injury in mice by modulating gut microbiota
- Journal of Army Medical University Vol. 47, Issue 20, Pages: 2495-2505(2025)
- 作者机构：
  
  陆军军医大学（第三军医大学）第二附属医院临床医学研究中心，重庆
- 作者简介：
  
  ZHOU Jiyin， E-mail： zhoujiyin@gmail.com
- 基金信息：
- DOI：10.16016/j.2097-0927.202508007
  CLC： R282.1;R372;R575.05
- Received：07 August 2025，
  
  Revised：2025-10-07，
  
  Accepted：08 October 2025，
  
  Published：30 October 2025
- 稿件说明：
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涂奠基，周吉银.小檗碱调节肠道菌群改善小鼠药物性肝损伤［J］.陆军军医大学学报，2025，47（20）：2495-2505.DOI：10.16016/j.2097-0927.202508007.

TU D J，ZHOU J Y.Berberine improves drug-induced liver injury in mice by modulating gut microbiota［J］.J Army Med Univ，2025，47（20）：2495-2505.DOI：10.16016/j.2097-0927.202508007.
涂奠基，周吉银.小檗碱调节肠道菌群改善小鼠药物性肝损伤［J］.陆军军医大学学报，2025，47（20）：2495-2505.DOI：10.16016/j.2097-0927.202508007. DOI：

TU D J，ZHOU J Y.Berberine improves drug-induced liver injury in mice by modulating gut microbiota［J］.J Army Med Univ，2025，47（20）：2495-2505.DOI：10.16016/j.2097-0927.202508007. DOI：

摘要

目的

探究小檗碱（berberine，BBR）缓解药物性肝损伤（drug-induced liver injury， DILI）小鼠的作用及小鼠肠道菌群的变化特征，明确BBR通过肠道菌群对DILI的改善机制。

方法

构建对乙酰氨基酚（acetaminophen， APAP）DILI动物模型，将12只C57BL/6J小鼠按体质量采用随机区组法分为2组（即APAP组和APAP-BBR组），每组6只，收集2组小鼠的血清及肝脏组织，检测灌胃BBR对DILI小鼠的血清酶学、炎症相关指标及肝脏病理的作用；收集2组小鼠的新鲜粪便，对粪便菌群进行16S测序，比较2组小鼠肠道微生物的α和β多样性和肠道菌群结构特征，运用Pearson法分析2组之间的差异菌与小鼠血清学指标之间的相关性。

结果

灌胃BBR显著降低了APAP诱导的血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平，改善了APAP诱导的肝细胞坏死比例。16S测序分析结果显示，APAP-BBR组相比于APAP组小鼠，α多样性的Chao1和Shanon指数无统计学差异，而β多样性有统计学差异（

0.05）；与APAP-BBR组比较，APAP组中

Alloprevotella

和

Ruminococcaceae_UCG_014

相对丰度明显升高（

0.05）；与APAP组比较，

Parabacteroides

在APAP-BBR组中相对丰度升高，且具有统计学差异（

0.05）。Pearson相关性分析表明，

Alloprevotella

与AST（

0.05）强相关，

Ruminococcaceae

与ALT、AST强相关（

0.05），

Parabacteroides

与ALT、AST强相关（

0.05）。

结论

灌胃BBR能够通过肠道菌群改变减缓DILI小鼠疾病的进展。

Abstract

Objective

To investigate the protective effects of berberine (BBR) against drug-induced liver injury (DILI) in mice and the change profiles in gut microbiota

and to elucidate the underlying mechanism by which BBR alleviates DILI through modulation of the gut microbiota.

Methods

Acetaminophen (APAP) administration was performed on C57BL/6J mice with or without pre-treatment of ampicillin-neomycin-metronidazole-vancomycin (ABX

depletion of gut microbiota) to establish a DILI model. Based on body weight

12 mice were randomly divided into an APAP group and a BBR group

with 6 animals in per group. Serum and liver tissue samples were collected from both groups to determine the effects of intragastrical administration of BBR on serum transaminase levels

inflammatory indicators

and liver histopathology. Fresh fecal samples were also collected to profile the gut microbiota using 16S rRNA gene sequencing. Then the alpha and beta diversity

as well as the overall microbial community structure

were compared between the 2 groups. Pearson correlation analysis was employed to analyze the relationships between differentially abundant bacteria and the serological indicators.

Results

Intragastrical administration of BBR significantly reduced APAP-induced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

and ameliorated the proportion of hepatocellular necrosis caused by APAP. The results of 16S rRNA gene sequencing revealed that there were no statistical differences in the alpha diversity indices (Chao1 and Shannon) between the APAP-BBR and APAP groups

but a significant difference was observed in beta diversity (

0.05). Compared to the APAP-BBR group

the relative abundances of

Alloprevotella

and

Ruminococcaceae_UCG_014

were significantly increased in the APAP group (

0.05). Conversely

the relative abundance of

Parabacteroides

was significantly higher in the APAP-BBR group than the APAP group (

0.05). Pearson correlation analysis demonstrated that

Alloprevotella

was strongly correlated with AST level (

0.05)

while both

Ruminococcaceae

and

Parabacteroides

showed strong correlations with ALT and AST levels (

0.05).

Conclusion

Intragastric administration of BBR can mitigate the progression of DILI in mice

potentially through modulating the gut microbiota.

关键词

Keywords

references

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