IADR Abstract Archives
Intestinal Microecology Alteration by Oral Antibiotics Promote OSCC Development
Objectives: The interference of oral antibiotics on the intestinal microbiota is serious and difficult to recover. Recent studies have shown that oral antibiotics have an impact on the progression of a variety of cancers and immunotherapy. The association between oral antibiotics and oral squamous cell carcinoma (OSCC), and the mechanisms underlying the effects of oral antibiotics on OSCC are unclear. We aimed to explore the possible mechanisms of how oral antibiotics affect OSCC.
Methods: BALB/c mouse model of OSCC was created by injection of SCC7 cells. The drinking water of OSCC mice contained ampicillin (1g/L), neomycin trisulfate (1g/L), metronidazole (1g/L), and vancomycin (500 mg/L) (4Abx, n=10). 16S rRNA sequencing and colorimetric assay were used to detect the alteration of microbiota, glutamate, and tyrosine in the gut. IHC was applied to detect the expression of necroptosis. Glutamate and tyrosine were applied in PBMCs and SCC7 cells to verify the in vivo results. Furthermore, the OSCC mice that had drunk 4Abx were treated with glutamic acid (n=6) or healthy mouse feces (n=6) by gavage.
Results: Oral antibiotics shifted microbiota and microbial metabolism in the gut of OSCC mice. Tyrosine in feces increased and glutamate decreased. Tyrosine upregulated the PD-1 expression of T cells, the proliferation of SCC7, and the expression of necroptosis-related proteins. IL-10 expression of CD11c+ cells was reduced by glutamic acid. The expression of necroptosis-related proteins was higher in OSCC mice with 4Abx treatment. Glutamate or healthy mouse feces by gavage could alleviate the tumor-promoting effect of 4Abx with the balance of microbial metabolism.
Conclusions: We identified the detrimental role of oral antibiotics in promoting OSCC development by altering the intestinal microbiota, microbial metabolism, and immune dysbiosis, implying the need for antibiotic stewardship in OSCC.
Methods: BALB/c mouse model of OSCC was created by injection of SCC7 cells. The drinking water of OSCC mice contained ampicillin (1g/L), neomycin trisulfate (1g/L), metronidazole (1g/L), and vancomycin (500 mg/L) (4Abx, n=10). 16S rRNA sequencing and colorimetric assay were used to detect the alteration of microbiota, glutamate, and tyrosine in the gut. IHC was applied to detect the expression of necroptosis. Glutamate and tyrosine were applied in PBMCs and SCC7 cells to verify the in vivo results. Furthermore, the OSCC mice that had drunk 4Abx were treated with glutamic acid (n=6) or healthy mouse feces (n=6) by gavage.
Results: Oral antibiotics shifted microbiota and microbial metabolism in the gut of OSCC mice. Tyrosine in feces increased and glutamate decreased. Tyrosine upregulated the PD-1 expression of T cells, the proliferation of SCC7, and the expression of necroptosis-related proteins. IL-10 expression of CD11c+ cells was reduced by glutamic acid. The expression of necroptosis-related proteins was higher in OSCC mice with 4Abx treatment. Glutamate or healthy mouse feces by gavage could alleviate the tumor-promoting effect of 4Abx with the balance of microbial metabolism.
Conclusions: We identified the detrimental role of oral antibiotics in promoting OSCC development by altering the intestinal microbiota, microbial metabolism, and immune dysbiosis, implying the need for antibiotic stewardship in OSCC.