Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model
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 <i>Escherichia coli</i> Nissle (EcN) 191...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Proceedings |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2504-3900/91/1/402 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849340287963365376 |
|---|---|
| author | Johnson Lok Valeria Iannone Carlos Gómez-Gallego Ruben Vazquez-Uribe Morten Otto Alexander Sommer Marjukka Kolehmainen Hani El-Nezami |
| author_facet | Johnson Lok Valeria Iannone Carlos Gómez-Gallego Ruben Vazquez-Uribe Morten Otto Alexander Sommer Marjukka Kolehmainen Hani El-Nezami |
| author_sort | Johnson Lok |
| collection | DOAJ |
| description | 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 <i>Escherichia coli</i> 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 (<i>Roseburia</i> sp.) and <i>Lactobacillus reuteri</i>. Mice receiving EcN-FGF19 had lower abundance of bacteria associated with intestinal inflammation (Coriobacteriia) and higher abundance of SCFA-producing bacteria (<i>Roseburia</i> sp. and <i>Blautia</i> 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. |
| format | Article |
| id | doaj-art-07d87654849d476bb88f5422f3e9c62d |
| institution | Kabale University |
| issn | 2504-3900 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Proceedings |
| spelling | doaj-art-07d87654849d476bb88f5422f3e9c62d2025-08-20T03:43:57ZengMDPI AGProceedings2504-39002024-03-0191140210.3390/proceedings2023091402Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice ModelJohnson Lok0Valeria Iannone1Carlos Gómez-Gallego2Ruben Vazquez-Uribe3Morten Otto Alexander Sommer4Marjukka Kolehmainen5Hani El-Nezami6Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, FinlandNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, DenmarkNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, DenmarkInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, FinlandInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, FinlandBackground 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 <i>Escherichia coli</i> 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 (<i>Roseburia</i> sp.) and <i>Lactobacillus reuteri</i>. Mice receiving EcN-FGF19 had lower abundance of bacteria associated with intestinal inflammation (Coriobacteriia) and higher abundance of SCFA-producing bacteria (<i>Roseburia</i> sp. and <i>Blautia</i> 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.https://www.mdpi.com/2504-3900/91/1/402advanced microbial therapeuticsmetabolic dysfunction-associated steatotic liver diseasemetabolic diseasegut microbiome |
| spellingShingle | Johnson Lok Valeria Iannone Carlos Gómez-Gallego Ruben Vazquez-Uribe Morten Otto Alexander Sommer Marjukka Kolehmainen Hani El-Nezami Engineered <i>Escherichia coli</i> 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 advanced microbial therapeutics metabolic dysfunction-associated steatotic liver disease metabolic disease gut microbiome |
| title | Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model |
| title_full | Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model |
| title_fullStr | Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model |
| title_full_unstemmed | Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model |
| title_short | Engineered <i>Escherichia coli</i> Nissle 1917 Expressing IGF1 and FGF19 Reduce Liver Fat Accumulation and Restore Microbial Equilibrium in a Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Model |
| title_sort | engineered i escherichia coli i nissle 1917 expressing igf1 and fgf19 reduce liver fat accumulation and restore microbial equilibrium in a metabolic dysfunction associated steatotic liver disease mice model |
| topic | advanced microbial therapeutics metabolic dysfunction-associated steatotic liver disease metabolic disease gut microbiome |
| url | https://www.mdpi.com/2504-3900/91/1/402 |
| work_keys_str_mv | AT johnsonlok engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel AT valeriaiannone engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel AT carlosgomezgallego engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel AT rubenvazquezuribe engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel AT mortenottoalexandersommer engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel AT marjukkakolehmainen engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel AT hanielnezami engineerediescherichiacoliinissle1917expressingigf1andfgf19reduceliverfataccumulationandrestoremicrobialequilibriuminametabolicdysfunctionassociatedsteatoticliverdiseasemicemodel |