{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:20:46Z","timestamp":1774862446819,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Research Program of Jiangsu","award":["BK20241761"],"award-info":[{"award-number":["BK20241761"]}]},{"name":"Third Level Talents of the \u201c333 High Level Talents Training Project\u201d in the sixth phase in Jiangsu"},{"name":"Top Talent Support Program for young and middle-aged people of Wuxi Health Committee","award":["BJ2023023"],"award-info":[{"award-number":["BJ2023023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Lung cancer is the most common malignancy worldwide and has the highest mortality rate. Although therapeutic approaches have improved over recent years, the clinical efficacy of lung cancer treatment remains limited. Therefore, there is an urgent need to develop novel and effective immunotherapeutic strategies for lung cancer. Methods: In this study, we constructed a novel bacterial complex vaccine (Neo-BCV, hereafter referred to as BCV) and investigated its anti-tumor effects and underlying mechanisms in a murine lung cancer model. We further explored the role of the gut microbiota, bile acid metabolism, and T-cell function in BCV-mediated anti-tumor immunity. In addition, we performed a preliminary evaluation of the clinical safety of BCV in human subjects. Results: BCV treatment significantly enhanced the infiltration of CD4+ and CD8+ T cells into the tumor immune microenvironment and promoted the secretion of anti-tumor effector molecules. Mechanistically, BCV markedly increased the abundance of Lactobacillus reuteri (L. reuteri) in the gut microbiota and reduced serum levels of taurocholic acid (TCA). Further experiments confirmed that L. reuteri directly degrades TCA, and decreased TCA levels restored the effector functions of CD4+ and CD8+ T cells. Conclusions: This study demonstrates that BCV remodels the gut microbiota and enhances anti-tumor immunity by regulating the L. reuteri\u2013TCA axis to restore T-cell function. This mechanism provides a new strategy for improving the tumor immune microenvironment and supports further investigation and development of BCV as a therapeutic candidate for lung cancer.<\/jats:p>","DOI":"10.3390\/vaccines14040310","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neo-BCV: A Novel Bacterial Complex Vaccine Reshaping the Gut Microbiota to Enhance the Antitumor Immune Response"],"prefix":"10.3390","volume":"14","author":[{"given":"Hairu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Oncology, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyun","family":"Man","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0679-4780","authenticated-orcid":false,"given":"Qingfeng","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kecheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Oncology Department, National Key Clinical Specialty (Oncology), Biomedical Translational Research Institute, Fuda Cancer Hospital, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyi","family":"Wang","sequence":"additional","affiliation":[{"name":"National Research Centre for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Research Unit of Hematologic Malignancies Genomics and Translational Research of Chinese Academy of Medical Sciences, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2855-8780","authenticated-orcid":false,"given":"Peihua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12943-023-01740-y","article-title":"Lung cancer immunotherapy: Progress, pitfalls, and promises","volume":"22","author":"Lahiri","year":"2023","journal-title":"Mol. 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