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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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<jats:sup>9<\/jats:sup> CFU each of aldafermin-expressing <jats:italic>Escherichia coli<\/jats:italic> Nissle (EcNA, <jats:italic>n<\/jats:italic>\u2009=\u20096); while the control groups received either 10<jats:sup>9<\/jats:sup>\u2009CFU\/gelatine cube of non-modified <jats:italic>Escherichia coli<\/jats:italic> Nissle (EcN, <jats:italic>n<\/jats:italic>\u2009=\u20096) or gelatin cube with no treatment (CTRL, <jats:italic>n<\/jats:italic>\u2009=\u20096). 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>After seven weeks of intervention, EcNA, when compared to CTRL group, induced smaller adipocytes (<jats:italic>p<\/jats:italic>-value\u2009=\u20090.0217 for diameter, <jats:italic>p<\/jats:italic>-value\u2009=\u20090.0386 for area). Gene Set Enrichment Analysis in eVAT showed significant upregulation of fatty acid metabolism (FDR-adjusted <jats:italic>p<\/jats:italic>-value\u2009=\u20090.001), oxidative phosphorylation (FDR-adjusted <jats:italic>p<\/jats:italic>-value\u2009&lt;\u20092.2e-16), peroxisome (FDR-adjusted <jats:italic>p<\/jats:italic>-value\u2009=\u20090.0185), and thermogenesis (FDR-adjusted <jats:italic>p<\/jats:italic>-value\u2009=\u20090.0199) 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 <jats:italic>Bcl6<\/jats:italic> and <jats:italic>Cnst<\/jats:italic> expression in both tissues when EcNA was compared to CTRL and EcN groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41366-025-01774-w","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T01:08:56Z","timestamp":1744247336000},"page":"1334-1344","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The effect of aldafermin expressing-Escherichia coli Nissle 1917 along with dietary change on visceral adipose tissue in MASLD mouse model"],"prefix":"10.1038","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2114-1366","authenticated-orcid":false,"given":"Valeria","family":"Iannone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Vaittinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-1827","authenticated-orcid":false,"given":"Carlos","family":"G\u00f3mez-Gallego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-0657","authenticated-orcid":false,"given":"Santtu","family":"Mikkonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson","family":"Lok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"D\u2019Auria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9800-0409","authenticated-orcid":false,"given":"Ruben","family":"Vazquez-Uribe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Tikkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Otto Alexander","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"El-Nezami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-2538","authenticated-orcid":false,"given":"Marjukka","family":"Kolehmainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"1774_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/S2468-1253(22)00375-2","volume":"8","author":"SMA Francque","year":"2023","unstructured":"Francque SMA, Dirinck E. 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