Engineered Escherichia coli Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model †
by
, , , and
Johnson Lok
1,*
,
Valeria Iannone
1,
Carlos Gómez-Gallego
1,
Ruben Vazquez-Uribe
2,
Morten Otto Alexander Sommer
2,
Marjukka Kolehmainen
1
and
Hani El-Nezami
1,3 1
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
2
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark
3
School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, China
*
Author to whom correspondence should be addressed.
†
Presented at the 14th European Nutrition Conference FENS 2023, Belgrade, Serbia, 14–17 November 2023.
Proceedings 2023, 91(1), 402; https://doi.org/10.3390/proceedings2023091402
Published: 8 March 2024
(This article belongs to the Proceedings of The 14th European Nutrition Conference FENS 2023)
Abstract
:Background and objectives: Endocrine dysregulation and intestinal microbiota unbalance are commonly associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the effectiveness of engineered probiotic Escherichia coli Nissle (EcN) 1917 expressing various hormones (IGF1, GLP-1, FGF19, Adiponectin) downregulated in MASLD as a potential therapeutic. Methods: 41 C57BL/6J mice underwent 14 weeks of a high-fat diet intervention for MASLD development. The mice were then separated into seven groups and underwent 7 weeks of probiotic intervention while under the control diet. The mice were grouped as follows: (1) without probiotic; (2) EcN without hormone expression; (3–6) EcN expressing IGF1, GLP-1, FGF19, and Adiponectin, respectively; and (7) liraglutide treatment. Liver fat was measured using MRI and the Oil-Red-O staining of liver histological samples. 16s rRNA sequencing was used to investigate the bacterial composition in mice cecum. Results: Mice receiving EcN expressing IGF1, GLP-1, and FGF19 were effective at reducing liver fat accumulation. Microbiota compositions were different between groups, and the microbial communities of mice receiving EcN expressing IGF1 and FGF19 had higher observed richness. Mice receiving EcN-IGF1 had lower abundance of sulfate-reducing bacteria (Desulfobacterota) associated with gut inflammation and higher abundance of butyrate-producing bacteria (Roseburia sp.) and Lactobacillus reuteri. Mice receiving EcN-FGF19 had lower abundance of bacteria associated with intestinal inflammation (Coriobacteriia) and higher abundance of SCFA-producing bacteria (Roseburia sp. and Blautia sp.) and plasma propionate levels. Discussion: EcN expressing IGF1 and FGF19 have the potential to reduce liver fat accumulation and restore microbial equilibrium. This may be a combined effect of hormones and EcN, as a probiotic, thereby improving gut endocrine and immune functions.
Author Contributions
Conceptualization: J.L., V.I., C.G.-G., R.V.-U., M.O.A.S., M.K. and H.E.-N.; data curation and formal analysis: J.L., V.I. and C.G.-G.; writing—original draft preparation, J.L.; writing—review and editing, J.L., V.I., C.G.-G., R.V.-U., M.O.A.S., M.K. and H.E.-N.; supervision, C.G.-G., M.O.A.S., M.K. and H.E.-N.; funding acquisition, M.O.A.S., M.K. and H.E.-N. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by the ITN Marie Curie BestTreat-Building a Gut Microbiome Engineering Toolbox for In Situ Therapeutic Treatments for Non-alcoholic Fatty Liver Disease (grant number 813781), the Novo Nordisk Foundation, NNF grant numbers NNF20CC0035580, NNF21OC0070455, and NNF22OC0081058.
Institutional Review Board Statement
The animal study protocol was approved by the Ethics Committee of National Ethics Committee for Animal Experiments in Finland (license number: ESAVI/21371/2019, date of approval: 24 September 2019).
Informed Consent Statement
Not applicable.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors on request.
Conflicts of Interest
J.L., V.I., C.G.-G., R.V.-U., M.O.A.S., M.K. and H.E.-N. are inventors on a patent filed by Technical University of Denmark and University of Eastern Finland on the therapeutic effect of the engineered strain.
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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MDPI and ACS Style
Lok, J.; Iannone, V.; Gómez-Gallego, C.; Vazquez-Uribe, R.; Sommer, M.O.A.; Kolehmainen, M.; El-Nezami, H. Engineered Escherichia coli Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model. Proceedings 2023, 91, 402. https://doi.org/10.3390/proceedings2023091402
AMA Style
Lok J, Iannone V, Gómez-Gallego C, Vazquez-Uribe R, Sommer MOA, Kolehmainen M, El-Nezami H. Engineered Escherichia coli Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model. Proceedings. 2023; 91(1):402. https://doi.org/10.3390/proceedings2023091402
Chicago/Turabian StyleLok, Johnson, Valeria Iannone, Carlos Gómez-Gallego, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer, Marjukka Kolehmainen, and Hani El-Nezami. 2023. "Engineered Escherichia coli Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model" Proceedings 91, no. 1: 402. https://doi.org/10.3390/proceedings2023091402
