Short-chain fatty acids alleviate cholestatic liver injury by improving gut microbiota and bile acid metabolism

Cholestasis, characterized by the obstruction of bile flow and the accumulation of bile acids, can lead to severe liver damage. Current treatments, such as ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), are limited in effectiveness and have significant side effects, underscoring the need for new therapies. In our study, we investigated the effects of short-chain fatty acids (SCFAs) as a treatment in a mouse model of cholestasis induced by α-naphthylisothiocyanate (ANIT). Our findings demonstrated that SCFAs improved liver function, as indicated by reductions in liver function markers, decreased necrosis, and reduced bile duct proliferation and inflammation. Furthermore, SCFAs enhanced intestinal barrier function and increased the abundance of beneficial gut bacteria, such as Akkermansia muciniphila (A. muciniphila). SCFAs also triggered the FXR-Fgf15-Cyp7a1 pathway, reducing bile acid synthesis and improving bile acid metabolism. These findings indicate that SCFAs could offer a viable new treatment strategy for cholestatic liver conditions by improving gut-liver interactions, stabilizing bile acid metabolism, and alleviating inflammation.

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Publication Details

Journal
International Immunopharmacology
Published
2025-04-06
DOI
https://doi.org/10.1016/j.intimp.2025.114564
Citations
9
Primary Topic
Diet and metabolism studies
Type
article
Field-Weighted Citation Impact
10.48
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article

Short-chain fatty acids alleviate cholestatic liver injury by improving gut microbiota and bile acid metabolism

Ruimeng Zhang, Zhan Yang, Zhuohan Zhang, Yanan Hu et al.
9 citations
International Immunopharmacology
Diet and metabolism studies
10.48
article

Short-chain fatty acids alleviate cholestatic liver injury by improving gut microbiota and bile acid metabolism

Ruimeng Zhang, Zhan Yang, Zhuohan Zhang, Yanan Hu, Xuewei Sun, Zihan Wu, Lunbiao Cui, Chengliang Tang, Shuang Song, Xinrui Zhang, Mingmin Zhang, Jin Zhu, Xiaojun Yang, Lu Han, Mingyan Zhang, Qian Cui, Wenjing Wang
article en
9 citations

Abstract

Cholestasis, characterized by the obstruction of bile flow and the accumulation of bile acids, can lead to severe liver damage. Current treatments, such as ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), are limited in effectiveness and have significant side effects, underscoring the need for new therapies. In our study, we investigated the effects of short-chain fatty acids (SCFAs) as a treatment in a mouse model of cholestasis induced by α-naphthylisothiocyanate (ANIT). Our findings demonstrated that SCFAs improved liver function, as indicated by reductions in liver function markers, decreased necrosis, and reduced bile duct proliferation and inflammation. Furthermore, SCFAs enhanced intestinal barrier function and increased the abundance of beneficial gut bacteria, such as Akkermansia muciniphila (A. muciniphila). SCFAs also triggered the FXR-Fgf15-Cyp7a1 pathway, reducing bile acid synthesis and improving bile acid metabolism. These findings indicate that SCFAs could offer a viable new treatment strategy for cholestatic liver conditions by improving gut-liver interactions, stabilizing bile acid metabolism, and alleviating inflammation.

International ImmunopharmacologyVol. 154
Nanjing University of Chinese Medicine (CN), People 's Liberation Army 451 Hospital (CN), Huadong Hospital (CN), Sozvezdie (Russia) (RU), Yili Friendship Hospital (CN), Jiangsu Provincial Center for Disease Control and Prevention (CN), Second Affiliated Hospital of Nanjing Medical University (CN), Huadong Medical Institute of Biotechniques, Nanjing Medical University (CN)
Zero hunger
Openalex Percentile: Top 2%
Diet and metabolism studies
10.48
DOIOpen Access PDFOpenAlex
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