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While bacterial\u2010derived metabolites are increasingly recognized as key mediators, their specific roles in interkingdom crosstalk remain underexplored. Here, we develop a programmable probiotic platform leveraging\n                    <jats:italic>Lactobacillus gasseri<\/jats:italic>\n                    (LG)\u2010tumor metabolic interplay to potentiate bladder cancer therapy. The selected LG strain demonstrates superior tumor\u2010colonizing ability and intrinsic H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \/lactate biosynthesis, creating an optimal tumor microenvironment for hemoglobin\u2010modified MnOx nanoparticles to enhance chemodynamic therapy efficacy. Mechanistically, microbial metabolites, including L\u2010leucine, orchestrate neutrophil phenotypic reprogramming by suppressing pro\u2010angiogenic dcTRAIL\u2010R1\n                    <jats:sup>+<\/jats:sup>\n                    neutrophils while activating antigen\u2010presenting CD74\n                    <jats:sup>+<\/jats:sup>\n                    neutrophil populations. The engineered system elicites coordinated immunomodulation through multiple mechanisms: (1) promoting dendritic cell maturation, (2) increasing CD74\n                    <jats:sup>+<\/jats:sup>\n                    neutrophil populations, (3) inducing macrophage polarization from M2 to M1 phenotypes, and (4) enhancing tumor infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and natural killer cells. This study reveals that bacteria\u2010tumor metabolic crosstalk upregulates beneficial metabolites, notably leucine, which promotes phenotypic reprogramming of neutrophils toward the antigen\u2011presenting CD74\n                    <jats:sup>+<\/jats:sup>\n                    subset, thereby bridging innate metabolic regulation with adaptive antitumor immunity. This finding goes beyond the material\u2010centric logic of previous probiotic\u2010nanomaterial systems and establishes a metabolism\u2010centric framework for bacteria\u2011mediated cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.74353","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:11:12Z","timestamp":1785507072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic Reprogramming by Engineered Probiotics Potentiates Tumor Chemodynamic Immunotherapy"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-1897","authenticated-orcid":false,"given":"Kai","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Li","sequence":"additional","affiliation":[{"name":"China Institute of Functional Nano and Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyu","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-6534","authenticated-orcid":false,"given":"Yongkang","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore 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