Gut microbiome-mediated monocytes promote liver metastasis

Int Immunopharmacol. 2024 May 30:133:111877. doi: 10.1016/j.intimp.2024.111877. Epub 2024 Apr 11.

Abstract

The gut microbiome plays an important role in tumor growth by regulating immune cell function. However, the role of the gut microbiome-mediated monocytes in liver metastasis remains unclear. In this study, we found that fecal microbiome transplantation (FMT) from the stool of patients with liver metastasis (LM) significantly promoted liver metastasis compared with healthy donors (HD). Monocytes were upregulated in liver tissues by the CCL2/CCR2 axis in LM patients' stool transplanted mouse model. CCL2/CCR2 inhibition and monocyte depletion significantly suppress liver metastasis. FMT using LM patients' stool enhanced the plasma lipopolysaccharides (LPS) concentration. The LPS/TLR4 signaling pathway is crucial for gut microbiome-mediated liver metastasis. These results indicated that monocytes contribute to liver metastasis via the CCL2/CCR2 axis.

Keywords: CCL2/CCR2; Gut microbiome; LPS/TLR4; Liver metastasis; Monocytes.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemokine CCL2* / metabolism
  • Fecal Microbiota Transplantation*
  • Female
  • Gastrointestinal Microbiome* / immunology
  • Humans
  • Lipopolysaccharides / immunology
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / secondary
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes* / immunology
  • Receptors, CCR2* / metabolism
  • Signal Transduction
  • Toll-Like Receptor 4* / metabolism

Substances

  • Chemokine CCL2
  • Receptors, CCR2
  • Toll-Like Receptor 4
  • Lipopolysaccharides