Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets

Yongxin Zhang; Yameng Liu; Xinyu Liang; Yingquan Wen; Jingjie Zhao; Yong He; Qing Xie; Cen Xie

doi:10.1016/j.apsb.2025.08.028

Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets

Acta Pharm Sin B. 2025 Nov;15(11):5515-5536. doi: 10.1016/j.apsb.2025.08.028. Epub 2025 Sep 3.

Authors

Yongxin Zhang^{1

2}, Yameng Liu^{1

2}, Xinyu Liang^{1

3}, Yingquan Wen^{1

4}, Jingjie Zhao^{1

5

6}, Yong He^{1

2}, Qing Xie⁷, Cen Xie^{1

2

5

7}

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
⁴ School of Life Sciences and Technology, Tongji University, Shanghai, 200127, China.
⁵ School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
⁶ Lingang Laboratory, Shanghai 200031, China.
⁷ Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Abstract

The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.

Keywords: Barrier dysfunction; Barrier integrity detection; Dysbiosis; Factors affecting intestinal integrity; Gut and liver diseases; Intestinal barrier; Therapeutic targeting barrier repair; Tight junction.

Publication types

Review