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Therefore, exogenous degradation or conversion of excessive BCAAs may help alleviate diseases caused by BCAA accumulation, such as maple syrup urine disease. This study utilized synthetic biology approaches to engineer two strains for efficient BCAA catabolism successfully\u2014ECN\u2010Deg and ECN\u2010Tra\u2014by integrating specific metabolic pathways into the chassis strain,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Nissle 1917 (ECN). ECN\u2010Deg integrates a metabolic module for BCAA degradation, while ECN\u2010Tra integrates a metabolic module for BCAA transformation. Both engineered strains demonstrate efficient BCAA catabolism in vitro and in vivo. In a high\u2010BCAA mouse model, ECN\u2010Deg and ECN\u2010Tra alleviated liver and ileal damage caused by excessive BCAAs and reduced systemic inflammation levels. Furthermore, ECN\u2010Deg and ECN\u2010Tra were able to modulate the gut microbiota, increasing the richness of\n                    <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    and\n                    <jats:italic>Mucispirillum schaedleri<\/jats:italic>\n                    , which are associated with health benefits. Additionally, they reduced the richness of the pathogenic bacterium\n                    <jats:italic>Streptococcus pasteurianus<\/jats:italic>\n                    . Thus, this study lays the foundation for the development of probiotics for the treatment of BCAAs metabolic disorders and BCAAs\u2010related chronic diseases.\n                  <\/jats:p>","DOI":"10.1002\/btm2.70075","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T11:29:51Z","timestamp":1757935791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design and pharmacodynamic study of live biotherapeutic products with efficient degradation of branched\u2010chain amino acids"],"prefix":"10.1002","volume":"10","author":[{"given":"Zhaowei","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai 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