Fecal microbiota transplantation regulates the composition of intestinal-derived estrogens and their metabolites : a study on the correlation with non-alcoholic fatty liver disease

Acta Universitatis Medicinalis Anhui 2025, 08, v.60 1423-1431     font:big middle small

Found programs: National Natural Science Foundation of China (No. 82370591) ; Natural Science Foundation of Anhui Province (No. 2308085MH242) ; Basic and Clinical Collaborative Research Enhancement Project of Anhui Medical University (No. 2021xkjT023)

Authors:Li Wanli1 , Qi Xueping2 , Cong Shuqi1 , Zhang Wanting1 , Zhang Tingting1 , Wang Sheng3 , Fang Haiming4 , Wen Jiyue1 , Wang Jiajia1

Keywords:non-alcoholic fatty liver disease ; gut microbiota; fecal microbiota transplantation ; estrogens;metabo- lomics

DOI:10.19405/j.cnki.issn1000-1492.2025.08.009

〔Abstract〕 To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) . Methods Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method. Results The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 . Conclusion FMT restores the disrupted composition of intestinal EMs and improves NAFLD.