Background: Emerging research has shown that cancer microbiome and its metabolites significantly impact cancer development, progression, and response to therapy, including immunotherapies. Nevertheless, in mice and humans, the combination of broad-spectrum antibiotics with immunotherapy resulted in worse overall outcomes. This indicates the requirement for alternate strategies, such as bacteriophage-based therapy. Our laboratory has shown that the Fusobacterium nucleatum (F.nucleatum), a constituent of the oral microbiota and a recognized oncomicrobe, is able to infect human and murine gastric cancer cells and promote their proliferation. Importantly, while the treatment of cancer cell/F.nucleatum co-cultures with antibiotic does not reduce proliferation, while the addition of FNU1, a F.nucleatum-specific bacteriophage reversed the outcome.
Aims: To investigate the impact of F. nucleatum infection on the composition of the tumour microenvironment and the efficacy of FNU1 therapy in eradicating tumour-associated F. nucleatum.
Method: Gastric tumour tissue from murine gastric cancer organoids induced 8–10-week-old immune-competent C57BL/6 mice were processed and stained with lectin and analy the F. nucleatum binding protein (GAL-GaLNac) using confocal microscopy and flow cytometry analysis. Further, murine gastric cancer organoid and human gastric cancer cell were infected with F. nucleatum to perform additional downstream analysis. ImageJ and graphPad Prism 9.0 software were used for data analysis.
Result: Our finding has revealed that early autochotuones gastiric tumours and murine gastric cancer organoid express a significant amount of F. nucleatum binding protein (GAL-GaLNac). Furthermore, confocal, 3D spheroid image and and flow cytometry analysis have demonstrated that F. nucleatum is able to infect human gastric cancer cells and murine gastric tumour organoids.
Conclusion: These findings suggest that gastric tumours express significant amount of unique sugar molecules that able to facilitate the binding of fap2 molecule present in F. nucleatum, leading to increased cancer cell proliferation, progression, and resistance to chemotherapy. Furthermore, infected cell have increased cells proliferation and migration compared with uninfected cells.