Neo-BCV: A Novel Bacterial Complex Vaccine Reshaping the Gut Microbiota to Enhance the Antitumor Immune Response

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–TCA 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.