Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice

Biochem Biophys Res Commun. 2017 Jun 24;488(2):418-424. doi: 10.1016/j.bbrc.2017.05.071. Epub 2017 May 12.

Abstract

Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation.

Keywords: Antigen-presenting cells; Gut microbiota; LPS; Tumor immune microenvironment.

MeSH terms

  • Adenomatous Polyposis Coli Protein / antagonists & inhibitors*
  • Adenomatous Polyposis Coli Protein / immunology
  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / immunology
  • Disease Models, Animal
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Injections, Subcutaneous
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Th1 Cells / drug effects
  • Th1 Cells / immunology

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Anti-Bacterial Agents
  • Cytokines
  • Lipopolysaccharides