The Gut Commensal Bacteria Veillonella parvula-Induced Neutrophil Activation Mediates Antitumor Activity

Recent scientific efforts have focused on identifying commensal microbiota with antitumor activity, yet most cancer studies remain limited to taxonomic associations or treatment-induced microbial changes, with only a few addressing underlying mechanisms. These mechanistic studies have focused mainly on lymphoid cells such as CD8⁺ T cells, while neutrophil-mediated mechanisms have received little attention despite their abundance and functions. Here, we screened 16 taxa linked to positive responses to cancer immunotherapy and identified Veillonella parvula as effective in reducing tumor growth in a murine model. Using single-cell transcriptomics and flow cytometry, we show that V. parvula reshapes the tumor microenvironment by promoting infiltration of neutrophil subsets that secrete reactive oxygen and nitrogen species, driving tumor cell death. We further identify Vpar0143, a ferritin Dps family protein, as the bacterial effector responsible for neutrophil activation and the antitumor effect. Together, these findings reveal a commensal–neutrophil axis harnessable for microbe-based cancer therapy.