2. Academic Validation
  3. Alteration of intestinal microecology by oral antibiotics promotes oral squamous cell carcinoma development

Alteration of intestinal microecology by oral antibiotics promotes oral squamous cell carcinoma development

  • Mol Immunol. 2022 Sep;149:94-106. doi: 10.1016/j.molimm.2022.06.013.
Wei Wei 1,  Jia Li 1,  Fan Liu 2,  Miaomiao Wu 1,  Kaixin Xiong 1,  Qing He 3,  Bo Zhang 4,  Ye Deng 3,  Yan Li 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
  • 2 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Nursing department, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
  • 3 CAS Key Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 4 Department of Stomatology, Minda Hospital of Hubei Minzu University, Enshi 445000, China.
  • 5 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: feifeiliyan@163.com.
PMID: 35803000 DOI: 10.1016/j.molimm.2022.06.013
Abstract

Oral Antibiotics can influence cancers and immunotherapy by interfering with the intestinal microbiota. However, the association between oral Antibiotics and oral squamous cell carcinoma (OSCC) as well as the mechanisms underlying the effects of oral Antibiotics on OSCC remain unclear. Here, we found that oral Antibiotics cocktail (4Abx) promoted the tumor development and shifted the microbiota, decreasing the abundance of probiotic bacteria, and altered microbial metabolism in the gut of OSCC mice, increasing tyrosine and decreasing glutamate levels. In vitro experiments showed that tyrosine upregulated the PD-1 expression in T cells, SCC7 cell proliferation, and Necroptosis expression. IL-10 expression level in CD11c+ cells was reduced by glutamate. Furthermore, the expression of the necroptosis-related proteins, including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and Mixed Lineage Kinase domain-like (MLKL), was higher in the OSCC mice treated with 4Abx. Supplementation with glutamate or healthy mouse feces by gavage alleviated the tumor-promoting effect of 4Abx with restored balance of microbial metabolism. Overall, we identified the detrimental role of oral Antibiotics in promoting OSCC development through altered intestinal microbiota, microbial metabolism, and immune dysbiosis, implying the need for Antibiotic stewardship in OSCC treatment.

Keywords

Antibiotics; Glutamate; Microbiota; Necroptosis; Oral squamous cell carcinoma; Tyrosine.

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