Advanced Microbiome Therapeutics Accelerate MASLD Recovery by Restoring Intestinal Microbiota Equilibrium and the Gut-Liver Axis in a Mouse Model
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 <i>Escherichia coli</i> Nissle 1917 expressing IGF1 (EcNI) or aldafermin (EcNA), and control groups received <i>E. coli</i> 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.
Authors
- Hani El‐Nezami (ORCID: https://orcid.org/0000-0001-6700-4346)
- Emily Kwun Kwan Lo (ORCID: https://orcid.org/0000-0001-9258-0716)
- Valeria Iannone (ORCID: https://orcid.org/0000-0003-2114-1366)
- Ursula Schwab (ORCID: https://orcid.org/0000-0003-1838-7525)
- Marjukka Kolehmainen (ORCID: https://orcid.org/0000-0002-3770-2538)
- Carlos Gómez-Gallego (ORCID: https://orcid.org/0000-0003-0219-1827)
- Kati Hanhineva (ORCID: https://orcid.org/0000-0001-6834-7375)
- Congjia Chen (ORCID: https://orcid.org/0009-0004-6800-3184)
- Mikko I. Kettunen (ORCID: https://orcid.org/0000-0002-2004-660X)
- Ruben Vazquez-Uribe (ORCID: https://orcid.org/0000-0002-9800-0409)
- Morten Otto Alexander Sommer (ORCID: https://orcid.org/0000-0003-4005-5674)
- Otto Savolainen
- Ambrin Farizah Babu (ORCID: https://orcid.org/0000-0001-5698-1707)
- Johnson Lok (ORCID: https://orcid.org/0000-0002-0247-8118)
- Troels Holger Vaaben
Institutions
- University of Turku (FI)
- University of Eastern Finland (FI)
- Novo Nordisk Foundation (DK)
- Vlaams Instituut voor Biotechnologie (BE)
- Kuopio University Hospital (FI)
- Finland University (FI)
- Institute for Molecular Science (JP)
- Delfin Technologies (Finland) (FI)
- Chalmers University of Technology (SE)
- University of Hong Kong (HK)
- Thermo Fisher Scientific (Norway) (NO)
Publication Details
- Journal
- Journal of Agricultural and Food Chemistry
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1021/acs.jafc.5c01674
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Academy of Finland
- Novo Nordisk Fonden
- HORIZON EUROPE Marie Sklodowska-Curie Actions