{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:58Z","timestamp":1787894338056,"version":"build-2784847793"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Colorectal cancer liver metastasis (CRLM) develops in a hepatic niche where tumor cells encounter organ\u2011specific microbial, metabolic, and immune constraints. The role of intratumoral bacteria in this metastatic ecosystem remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed tumor and peritumoral tissues from 20 patients with non\u2011metastatic colorectal cancer (CRC) and 20 patients with CRLM by 5R 16S rDNA sequencing, untargeted metabolomics, and functional assays. Public datasets were used for single\u2011cell analysis of the tumor immune microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Primary colorectal lesions and paired liver metastases showed distinct microbial structures. Liver metastatic lesions had lower microbial diversity, and 73 genera differed between CRLM primary tumors and liver metastases.\n                      <jats:italic>Bacillus<\/jats:italic>\n                      was enriched in metastatic tumors and was associated with fatty\u2011acid\u2011related microbial pathways, serum CEA and CA19\u20119 levels, and lipid\u2011related metabolites that accumulated in liver metastases. Bacillus supernatant increased SW480 and SW620 cell migration and proliferation\n                      <jats:italic>in vitro<\/jats:italic>\n                      , with the strongest activity at a multiplicity of infection (MOI)\u2011equivalent of 20. In an intrasplenic CRLM model, viable\n                      <jats:italic>Bacillus<\/jats:italic>\n                      and Bacillus supernatant increased metastatic tumor growth, whereas antibiotic intervention reduced this effect. Metabolomic profiling detected enrichment of lipids and lipid\u2011like molecules, including carnitine\u2011 and bile\u2011acid\u2011related metabolites, in liver metastatic lesions. Single\u2011cell analysis of public datasets showed remodeling of the tumor immune microenvironment (TIME) and identified APOE\u207a macrophages as lipid\u2011associated myeloid cells with broad ligand\u2011receptor communication with epithelial, immune, and stromal compartments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Together, these findings provide evidence that\n                      <jats:italic>Bacillus<\/jats:italic>\n                      promotes metastatic phenotypes and reveal associations among intratumoral\n                      <jats:italic>Bacillus<\/jats:italic>\n                      , lipid\u2011related metabolic alterations, and APOE\n                      <jats:sup>+<\/jats:sup>\n                      macrophage\u2011associated communication signatures in CRLM.\n                    <\/jats:p>\n           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