Advanced Microbiome Therapeutics Accelerate MASLD Recovery by Restoring Intestinal Microbiota Equilibrium and the Gut-Liver Axis in a Mouse Model
: Lok, Johnson; Chen, Congjia; Iannone, Valeria; Babu, Ambrin Farizah; Lo, Emily Kwun Kwan; Vazquez-Uribe, Ruben; Vaaben, Troels Holger; Kettunen, Mikko; Savolainen, Otto; Schwab, Ursula; Sommer, Morten Otto Alexander; Hanhineva, Kati; Kolehmainen, Marjukka; El-Nezami, Hani; Gomez-Gallego, Carlos
Publisher: American Chemical Society
: WASHINGTON
: 2025
: Journal of Agricultural and Food Chemistry
: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
: J AGR FOOD CHEM
: 73
: 24
: 15199
: 15214
: 16
: 0021-8561
: 1520-5118
DOI: https://doi.org/10.1021/acs.jafc.5c01674
: https://pubs.acs.org/doi/10.1021/acs.jafc.5c01674
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.
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This work was supported by the ITN Marie Curie BestTreat-Building a Gut Microbiome Engineering Toolbox for In Situ Therapeutic Treatments for Nonalcoholic Fatty Liver Disease (grant number 813781), The Cell2Eat (Research Council of Finland decision number 339184), the Novo Nordisk Foundation, NNF grant numbers NNF20CC0035580, NNF21OC0070455, and NNF22OC0081058. K.H. is supported by the Academy of Finland (grant no. 321716) and ERA-NET NEURON (grant no. 334814).
