Bacteroides thetaiotaomicron Improves Colorectal Cancer Prognosis by Remodeling the Immune Microenvironment

ABSTRACT Background Colorectal cancer (CRC) progression is closely associated with gut microbiota. Bacteroides thetaiotaomicron (B.theta), a key species in the human cecal and colonic microbiota, plays an incompletely defined role in CRC progression. Methods CRC animal models were established utilizing immunocompetent C57BL/6 mice and immunodeficient BALB/C nude mice. Histopathological changes were assessed by H&E staining. Immune cell infiltration was evaluated by IHC. CD8 + T cells and cancer cells were treated with B.theta culture supernatant. Cytokine secretion was measured by ELISA. Surface protein expression levels on CD8 + T cells and cancer cell apoptosis were analyzed by flow cytometry. CD8 + T cell proliferation was determined by the CFSE assay. Tumor‐killing activity of CD8 + T cells was assessed by LDH release assay. Results In C57BL/6 mice, B.theta suppressed tumor development and promoted T cell infiltration. However, B.theta had no significant impact on CRC progression in BALB/C nude mice. B.theta supernatant treatment did not affect CRC cell phenotypes, including viability, apoptosis, MHC‐I expression, and extracellular ATP levels. Conversely, B.theta supernatant upregulated CD69 and CD44 expression on CD8 + T cells, promoted IFN‐γ and TNF‐α secretion, enhanced proliferation, and consequently augmented their cytotoxicity against CRC cells. Conclusion B.theta suppresses malignant CRC progression by modulating host immune responses.