The effect of aldafermin expressing-Escherichia coli Nissle 1917 along with dietary change on visceral adipose tissue in MASLD mouse model.

BACKGROUND

Visceral adipose tissue (VAT) accumulation in obesity has been implicated as a key factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Apart from lifestyle change interventions, there is no effective therapy against MASLD. In this study, the effect of a novel microbial therapy along with dietary change on VAT and VAT-liver crosstalk was evaluated in a MASLD mouse model.

METHODS

MASLD was induced by feeding eighteen C57BL/6J male mice with the American Lifestyle-Induced Obesity diet for fourteen weeks. Subsequently, during the following seven weeks, all mice were switched to standard diet and the intervention group received single gelatine cubes containing 10 CFU each of aldafermin-expressing Escherichia coli Nissle (EcNA, n = 6); while the control groups received either 10 CFU/gelatine cube of non-modified Escherichia coli Nissle (EcN, n = 6) or gelatin cube with no treatment (CTRL, n = 6). The effect of EcNA on epididymal visceral adipose tissue (eVAT) morphology was evaluated by histology and the gene expression profile in eVAT and liver by RNA-sequencing analysis.

RESULTS

After seven weeks of intervention, EcNA, when compared to CTRL group, induced smaller adipocytes (p-value = 0.0217 for diameter, p-value = 0.0386 for area). Gene Set Enrichment Analysis in eVAT showed significant upregulation of fatty acid metabolism (FDR-adjusted p-value = 0.001), oxidative phosphorylation (FDR-adjusted p-value < 2.2e-16), peroxisome (FDR-adjusted p-value = 0.0185), and thermogenesis (FDR-adjusted p-value = 0.0199) pathways when EcNA was compared to EcN group. In addition, the impact of EcNA in eVAT-liver gene expression crosstalk was underlined by the upregulation of Bcl6 and Cnst expression in both tissues when EcNA was compared to CTRL and EcN groups.

CONCLUSIONS

These results support the beneficial effects of EcNA, along with dietary change intervention, in obesity-associated MASLD. This microbial therapy could potentially boost the improvements induced by dietary change in eVAT metabolism and its crosstalk with the liver.