2. Academic Validation
  3. Lactiplantibacillus plantarum attenuate gossypol-induced hepatic lipotoxicity by altering intestinal microbiota for enriching microbial tryptophan metabolites in Nile tilapia (Oreochromis niloticus)

Lactiplantibacillus plantarum attenuate gossypol-induced hepatic lipotoxicity by altering intestinal microbiota for enriching microbial tryptophan metabolites in Nile tilapia (Oreochromis niloticus)

  • Microbiome. 2025 Aug 4;13(1):180. doi: 10.1186/s40168-025-02172-0.
Fei-Fei Ding # 1,  Nan-Nan Zhou # 1,  Yue-Jian Mao 2,  Jing Yang 2,  Samwel M Limbu 3,  Jorge Galindo-Villegas 4,  Zhen-Yu Du 1,  Mei-Ling Zhang 5
Affiliations

Affiliations

  • 1 School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • 2 Global R&D Innovation Center, Inner Mongolia Mengniu Dairy (Group) Co. Ltd, Hohhot, Inner Mongolia, 750336, China.
  • 3 Department of Aquaculture Technology, School of Aquatic Sciences and Fisheries Technology, University of Dar Es Salaam, P. O. Box 60091, Dar Es Salaam, Tanzania.
  • 4 Department of Genomics, Faculty of Biosciences and Aquaculture, Nord University, Bodø, 8049, Norway.
  • 5 School of Life Sciences, East China Normal University, Shanghai, 200241, China. mlzhang@bio.ecnu.edu.cn.
  • # Contributed equally.
PMID: 40759977 DOI: 10.1186/s40168-025-02172-0
Abstract

Background: Free fatty acids (FFAs) are the main cause of fatty liver disease, which can be alleviated by modulation of intestinal microbiota. Lactiplantibacillus plantarum plays a key role in maintaining liver health, but the underlying mechanism remains unclear.

Results: Here, a strain affiliated to Lactiplantibacillus plantarum was isolated from the intestine of Nile tilapia (Oreochromis niloticus). We used a gossypol-induced fatty liver disease model, which only increased the FFAs level in liver, to investigate the effectiveness of L. plantarum (YC17) in alleviating FFAs-induced lipotoxicity liver injury. We found that dietary gossypol (GOS) induced a significant increase of FFAs in liver, resulting in lipotoxicity in Nile tilapia compared to control. L. plantarum YC17 supplementation reduced FFAs content by restoring esterification process, and then relieved liver injury. Addition of L. plantarum YC17 effectively increased the abundances of Lactobacillus, Clostridium and Cetobacterium in fish intestine, as well as serum levels of the microbial tryptophan metabolites, notably indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). The addition of L. plantarum YC17 significantly inhibited P53 signaling pathway and up-regulated the expression of FFAs esterification genes. In vitro experiments demonstrated that IPA inhibited P53 through ubiquitination and enhanced FFAs esterification in an Aryl Hydrocarbon Receptor (Ahr) dependent manner.

Conclusion: The gut microbiota-derived tryptophan metabolites (IPA and IAA) alleviated FFAs induced lipotoxic liver injury by activating Ahr, which promoted P53 ubiquitination, leading to the enhanced FFAs esterification. Our findings demonstrated that gut microbial metabolites alleviated lipotoxicity by promoting the esterification of FFAs in the liver, offering new insights into the study of probiotics and microbial tryptophan metabolites in fatty liver disease. Video Abstract.

Keywords

Lactiplantibacillus plantarum; Free fatty acids; Gut microbiota; Lipotoxicity; Microbial tryptophan metabolites.

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