Journal Article

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

Zhang, Meiling, Limbu, Samwel M, Mao, Yue-Jian, Yang, Jing, Ding, Fei-Fei, Galindo-Villegas, Jorge, Zhou, Nan-Nan

2025

Overview

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.

• Publisher: BMC,BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Acetic acid / Animals / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Cichlids - metabolism / Cichlids - microbiology / Diet / Digestive system / Esterification / Fatty acids / Fatty liver / Fatty Liver - chemically induced / Fishes / Free fatty acids / Gastrointestinal Microbiome - drug effects / Gastrointestinal tract / Gossypol / Gossypol - toxicity / Gut microbiota / Health maintenance organizations / Indoleacetic acid / Intestinal microflora / Intestine / Intestines - microbiology / Laboratory animals / Lactiplantibacillus plantarum / Lactiplantibacillus plantarum - physiology / Ligands / Lipids / Lipotoxicity / Liver - drug effects / Liver - metabolism / Liver - pathology / Liver cancer / Liver diseases / Medical Microbiology / Metabolic disorders / Metabolites / Microbial Ecology / Microbial Genetics and Genomics / Microbial tryptophan metabolites / Microbiology / Microbiota / Microbiota (Symbiotic organisms) / Oreochromis niloticus / p53 Protein / Probiotics / Propionic acid / Serum levels / Signal transduction / Tilapia / Triglycerides / Tryptophan / Tryptophan - metabolism / Tumor proteins / Ubiquitination / Virology