Advanced Microbiome Therapeutics Accelerate MASLD Recovery by Restoring Intestinal Microbiota Equilibrium and the Gut-Liver Axis in a Mouse Model
Journal article, 2025
Gut microbiota dysbiosis and endocrine dysregulation are key players in metabolic dysfunction-associated steatotic liver disease (MASLD) development. This study evaluated whether advanced microbiome therapeutics can restore intestinal microbial equilibrium and gut-liver axis balance during MASLD recovery. MASLD was induced in mice using a high-fat, high-sugar diet, and then shifted to a standard diet, where intervention groups received engineered Escherichia coli Nissle 1917 expressing IGF1 (EcNI) or aldafermin (EcNA), and control groups received E. coli Nissle 1917 vehicle (EcN) or no microbial intervention (CTRL). EcNI and EcNA improved MASLD recovery compared to controls by lowering hepatic fat, plasma cholesterol, and body weight, while increasing bacterial diversity, plasma acetate, and propionate, and modulating particular microbial groups, potentially alleviating dysbiosis. Additionally, EcNI and EcNA downregulated acetyl-CoA, the steroid hormone biosynthesis pathway, and EcNA upregulated the pentose phosphate pathway and pyruvate, which are related to oxidative stress reduction. These results suggest that EcNI and EcNA are potential novel treatments for MASLD.
insulin-like growth factor 1
aldafermin
nonalcoholic fatty liver disease (NAFLD)
integrative multiomics
E. coli Nissle 1917
fibroblast growth factor 19
Author
Johnson Lok
University of Eastern Finland
Congjia Chen
The University of Hong Kong
Valeria Iannone
University of Eastern Finland
Ambrin Farizah Babu
Afekta Technologies
University of Eastern Finland
Emily Kwun Kwan Lo
The University of Hong Kong
Ruben Vazquez-Uribe
Flanders Interuniversity Institute for Biotechnology
Novo Nordisk Foundation
Troels Holger Vaaben
Novo Nordisk Foundation
Mikko Kettunen
University of Eastern Finland
Otto Savolainen
Chalmers, Life Sciences, Infrastructures
University of Eastern Finland
Ursula Schwab
University of Eastern Finland
Kuopio University Hospital
Morten Otto Alexander Sommer
Novo Nordisk Foundation
K. Hanhineva
University of Turku
Afekta Technologies
University of Eastern Finland
M. Kolehmainen
University of Eastern Finland
Hani El-Nezami
University of Eastern Finland
The University of Hong Kong
Carlos Gómez-Gallego
University of Eastern Finland
Journal of Agricultural and Food Chemistry
0021-8561 (ISSN) 1520-5118 (eISSN)
Vol. 73 24 15199-15214Subject Categories (SSIF 2025)
Medical Life Sciences
DOI
10.1021/acs.jafc.5c01674