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Nevertheless, leveraging the gut microbiome as an interventional strategy has recently gained traction, especially in patients on immune checkpoint inhibitor (ICI) therapy. Here, microbial\u2010derived double\u2010layered membrane vesicles are developed as adjuvants and cell\u2010free carriers, fused with cell\u2010penetrating peptide\u2010modified antigens, and encapsulated in an alginate\/chitosan\u2010microsystem to engineer oral vaccines. This design strategically harnesses the crosstalk between the gut microbiome and gut\u2010associated lymphoid tissues, driving dendritic cell maturation, plasma cell activation, and production of immune\u2010stimulatory cytokines within the mesenteric lymph nodes and lamina propria. In mouse prophylactic and therapeutic tumor models, the select\n                    <jats:italic>Bifidobacterium bifidum<\/jats:italic>\n                    \u2010derived oral vaccine combined with anti\u2010PD1 treatment enhances cytotoxic antitumor responses, along with Th1\u2010, Th17\u2010immunity, leading to potent tumor suppression, prolonged survival, and long\u2010term protection against tumor rechallenge. Mechanistically, the vaccine promotes interferon\u2010\u03b3\u2010producing T cells and antitumor efficacy with ICI therapy via the improved microbiota diversity and signaling metabolites, with an indole\u20103\u2010acetic\u2010acid (3IAA) enriched diet profoundly shaping T\u2010cell recruitment and differentiation. Our findings uncover a tryptophan metabolite\u2010driven immune axis that amplifies the specific antitumor immune response, redefining oral vaccines as a powerful tool for cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.75342","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:17:08Z","timestamp":1791893828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing the Bacterial Membrane\u2010Derived Oral Vaccine to Potentiate Antitumor Immunity and Metabolic Control of T Cells"],"prefix":"10.1002","author":[{"given":"Wenfei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy Institute of Metabolic Diseases and Pharmacotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Institute of Metabolic Diseases and Pharmacotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Institute of Metabolic Diseases and Pharmacotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3854-7314","authenticated-orcid":false,"given":"Gelin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Institute of Metabolic Diseases and Pharmacotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1588-1772","authenticated-orcid":false,"given":"Xiaoya","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute for NanoBioTechnology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyao","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute for NanoBioTechnology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6201-9338","authenticated-orcid":false,"given":"Yining","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Institute of Metabolic Diseases and Pharmacotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-4217","authenticated-orcid":false,"given":"Li","family":"Mo","sequence":"additional","affiliation":[{"name":"Center of Gerontology and Geriatrics National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-1664","authenticated-orcid":false,"given":"Xun","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of Pharmacy Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-4696","authenticated-orcid":false,"given":"Jinhan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Institute of Metabolic Diseases and Pharmacotherapy West China Hospital Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Advanced Drug Delivery and Release Systems Shandong Luye Pharmaceutical Co., Ltd  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"A Guide to Vaccinology: From Basic Principles to New Developments","volume":"21","author":"Pollard A. 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