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Background <p>High-alcohol-producing <i>Klebsiella pneumoniae</i> (HiAlc <i>Kpn</i>) can cause metabolic dysfunction-associated steatotic liver disease (MASLD) through sustained alcohol overflow in the microenvironment. As a probiotic, <i>Bifidobacterium bifidum</i> (<i>B. bifidum</i>) exhibits unique anti-inflammatory properties; however, whether and how it alleviate MASLD induced by HiAlc <i>Kpn</i> requires further investigation.</p> Methods <p>MASLD mouse model was constructed by gavage administration with HiAlc <i>Kpn</i> W14 to assess the therapeutic effect of <i>B. bifidum</i> CIP-01 in vivo. Cell infection models, metabolomics sequencing, and in vitro antibacterial assays were integrated to systematically elucidate the mechanism by which <i>B. bifidum</i> CIP-01 mitigates HiAlc <i>Kpn</i> W14-induced cell damage.</p> Results <p><i>B. bifidum</i> CIP-01 was able to ameliorate MASLD induced by HiAlc <i>Kpn</i> through a multi-target mechanism. Compared to pair-fed mice, HiAlc <i>Kpn</i> W14 disrupted gut barrier and promoted inflammatory cytokines release. While, supplementation with <i>B. bifidum</i> CIP-01 reversed these effects by a) restoring intestinal integrity via upregulating tight junction proteins (ZO-1/Occludin) and mucin protein MUC-2, reducing reactive oxidative stress (ROS) and apoptosis in colonic cells, and b) rescuing hepatic cytochrome P450 2E1 (CYP2E1)-driven oxidative injury (ROS/Caspase-3) while promoting mitochondrial <i>β</i>-oxidation, as well as c) directly suppressing HiAlc <i>Kpn</i> proliferation and biofilm formation. Metabolomics and 16S rRNA of fecal samples analyses revealed <i>B. bifidum</i> CIP-01-mediated metabolic regulation: depletion of toxic branched-chain amino acids (BCAAs) intermediates and restoration of energy homeostasis and antioxidant defense alongside increased short-chain fatty acids (SCFAs)-associated pathways.</p> Conclusion <p>Our findings highlight <i>B. bifidum</i> CIP-01 as a novel therapeutic candidate for HiAlc <i>Kpn</i>-induced MASLD, operating through a triad of pathogen suppression, gut–liver axis repair, and metabolic regulation.</p>

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Bifidobacterium bifidum CIP-01 attenuates metabolic dysfunction-associated steatotic liver disease induced by high-alcohol-producing Klebsiella pneumoniae

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Xue Ren,
  • Chao Yan,
  • Xuanfeng Liu,
  • Xinyu Jia,
  • Yujie Chen,
  • Hanqing Zhao,
  • Yanling Feng,
  • Guanhua Xue,
  • Jinghua Cui,
  • Yuehua Ke,
  • Lin Gan,
  • Junxia Feng,
  • Zheng Fan,
  • Tongtong Fu,
  • Ziying Xu,
  • Zihui Yu,
  • Yang Yang,
  • Rentao Yu,
  • Jing Yuan

摘要

Background

High-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) can cause metabolic dysfunction-associated steatotic liver disease (MASLD) through sustained alcohol overflow in the microenvironment. As a probiotic, Bifidobacterium bifidum (B. bifidum) exhibits unique anti-inflammatory properties; however, whether and how it alleviate MASLD induced by HiAlc Kpn requires further investigation.

Methods

MASLD mouse model was constructed by gavage administration with HiAlc Kpn W14 to assess the therapeutic effect of B. bifidum CIP-01 in vivo. Cell infection models, metabolomics sequencing, and in vitro antibacterial assays were integrated to systematically elucidate the mechanism by which B. bifidum CIP-01 mitigates HiAlc Kpn W14-induced cell damage.

Results

B. bifidum CIP-01 was able to ameliorate MASLD induced by HiAlc Kpn through a multi-target mechanism. Compared to pair-fed mice, HiAlc Kpn W14 disrupted gut barrier and promoted inflammatory cytokines release. While, supplementation with B. bifidum CIP-01 reversed these effects by a) restoring intestinal integrity via upregulating tight junction proteins (ZO-1/Occludin) and mucin protein MUC-2, reducing reactive oxidative stress (ROS) and apoptosis in colonic cells, and b) rescuing hepatic cytochrome P450 2E1 (CYP2E1)-driven oxidative injury (ROS/Caspase-3) while promoting mitochondrial β-oxidation, as well as c) directly suppressing HiAlc Kpn proliferation and biofilm formation. Metabolomics and 16S rRNA of fecal samples analyses revealed B. bifidum CIP-01-mediated metabolic regulation: depletion of toxic branched-chain amino acids (BCAAs) intermediates and restoration of energy homeostasis and antioxidant defense alongside increased short-chain fatty acids (SCFAs)-associated pathways.

Conclusion

Our findings highlight B. bifidum CIP-01 as a novel therapeutic candidate for HiAlc Kpn-induced MASLD, operating through a triad of pathogen suppression, gut–liver axis repair, and metabolic regulation.