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A Bioengineered Live Biotherapeutic Exploits Inflammation to Restore Gut Liver Brain Axis Function under Diet-Induced Stress

Created on 14 Jul 2026

Authors

Verdugo Meza, A., Josephson, J. K., Dadlani, H., Yuzbashian, E., Davidson-Hunt, A., Ishida, R., Ghosh, S., Gibson, D. L.

Abstract

Live biotherapeutic products (LBPs) show promise for treating metabolic and inflammatory diseases, but their efficacy is limited by poor persistence in inflamed gut environments. EcN::ttr is a LBP designed to harness inflammation and is effective in the treatment of acute and chronic colitis. Diet-induced gut dysfunction can drive metabolic and behavioural alterations, we evaluated how EcN::ttr protects mice fed a proinflammatory omega-6-rich diet. EcN::ttr improved insulin sensitivity, associated with increased hepatic insulin receptor expression and reduced GSK3{beta} activation and endoplasmic reticulum stress EcN::ttr-treated mice exhibited notable changes in the gut, including an improved pattern of occludin expression, accompanied by reduced serum LPS-binding protein, indicating protection against endotoxemia. Bile acid analysis revealed more abundant SBA in mice treated with EcN::ttr, along with specific beneficial modulation of bile acids influencing diarrhea and bile acid detoxification. Behavioural assessment highlighted a normalization of long-term memory along with a reduction of stress management behaviours. Altogether, EcN::ttr restores gut liver brain axis function through coordinated modulation of inflammation, barrier integrity, and bile acid metabolism.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 14 Jul 2026.

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