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.
E. coli Nissle 1917
nonalcoholic fatty liver disease (NAFLD)
aldafermin
integrative multiomics
fibroblast growth factor 19
insulin-like growth factor 1
Author
Johnson Lok
University of Eastern Finland
Congjia Chen
The University of Hong Kong
Valeria Iannone
University of Eastern Finland
Ambrin Farizah Babu
University of Eastern Finland
Afekta Technologies
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
University of Eastern Finland
Chalmers, Life Sciences, Infrastructures
Ursula Schwab
Kuopio University Hospital
University of Eastern Finland
Morten Otto Alexander Sommer
Novo Nordisk Foundation
K. Hanhineva
University of Turku
University of Eastern Finland
Afekta Technologies
M. Kolehmainen
University of Eastern Finland
Hani El-Nezami
The University of Hong Kong
University of Eastern Finland
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