biostudies-literatureUnknown18(1)Dong X<b>Background/Objectives</b>: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). <i>Akkermansia muciniphila</i> and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic <i>Lacticaseibacillus paracasei</i> L9 for targeted Amuc_1100 delivery. <b>Methods</b>: We engineered <i>Lc. paracasei</i> L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrityNutrients123https://www.ebi.ac.uk/biostudies/studies/S-EPMC12787787biostudies-literatureSubcellular Localization Dictates Therapeutic Function: Spatially Targeted Delivery of Amuc_1100 by Engineered <i>Lacticaseibacillus paracasei</i> L9 Enhances Intestinal Barrier in Colitis.PMC12787787Ge SZhao LDong XWang RZhang HZhang MMiao WZhai ZHao YAi LLin LfalseSubcellular Localization Dictates Therapeutic Function: Spatially Targeted Delivery of Amuc_1100 by Engineered <i>Lacticaseibacillus paracasei</i> L9 Enhances Intestinal Barrier in Colitis.<b>Background/Objectives</b>: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). <i>Akkermansia muciniphila</i> and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic <i>Lacticaseibacillus paracasei</i> L9 for targeted Amuc_1100 delivery. <b>Methods</b>: We engineered <i>Lc. paracasei</i> L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrity2025-01-01T00:00:00Z2025 Dec2026-06-09T03:10:56.599Z2026-06-09T03:07:27.168ZS-EPMC127877874151524010.3390/nu18010123