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To address this limitation, we developed an intelligent oral biologics platform centered on an engineered probiotic strain (\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Nissle 1917) capable of producing therapeutic IL\u201022 in situ, encapsulated within an inulin hydrogel to resist gastric degradation. Critically, we integrated a sonogenetic control module that enables non\u2010invasive, spatiotemporally precise activation of IL\u201022 expression in the gut via remote ultrasound stimulation. In MASH model, this targeted, on\u2010demand IL\u201022 delivery effectively remodeled the gut microbiota and improved intestinal barrier function. This led to significantly reduced portal lipopolysaccharide (LPS) levels, which in turn decreased hepatic IL\u20106 production. Mechanistically, this strategy inhibited the pathological overactivation of the PI3K\u2010AKT\u2010mTOR signaling pathway, thereby markedly ameliorating hepatic steatosis, inflammation, and fibrosis. Notably, by confining IL\u201022 production to the gut, this strategy completely circumvented the off\u2010target effects of conventional IL\u201022 therapy. We observed reversal of MASH\u2010associated cognitive impairment, highlighting systemic benefits of restoring gut\u2010liver axis homeostasis. This study establishes a transformative, multi\u2010beneficial MASH therapy paradigm by modulating the gut\u2010liver axis, offering a safe, effective, clinically translatable strategy.\n                  <\/jats:p>","DOI":"10.1002\/advs.78100","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:24:26Z","timestamp":1791516266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sonogenetic Control of Engineered Probiotics for the Treatment of MASH by Modulating the Gut\u2010Liver Axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7664-0819","authenticated-orcid":false,"given":"Chunya","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Ultrasound Institute of Ultrasound in Medicine and Engineering Zhongshan Hospital Fudan University  Shanghai 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