Metabolomics and metagenomics reveal the impact of æ T inhibition on gut microbiota and metabolism in periodontitis-promoting OSCC

During the process of periodontitis-promoting oral squamous cell carcinoma (OSCC), the periodontitis microbiota can facilitate OSCC development by activating gamma delta T cells. Inhibiting gamma delta T cells through immunotherapy has been shown to significantly alleviate various types of cancer. However, the underlying mechanism by which inhibiting gamma delta T cells influenced cancer treatment has not been fully elucidated. In this study, a mouse model of OSCC with periodontitis was established, and gamma delta T cells were inhibited by antibodies. Gut samples from the mice were collected and analyzed by metabolomics, metagenomics, and 16S rRNA. Integrative analysis of the gut metabolome and microbiome revealed that targeting gamma delta T resulted in changes in the levels of metabolites associated with cancer in the gut. Although there was no difference in the alpha diversity of microbiota, beta diversity was significantly different, with a more heterogeneous community structure in the mice receiving targeted gamma delta T immunotherapy. Statistical analysis of the gut microbiota at the species level revealed a significant enrichment of Lactobacillus murinus, which was significantly correlated with gamma delta T abundance. The functional analysis revealed that inhibiting gamma delta T could impact the functional gene. A comprehensive analysis revealed that L. murinus is especially associated with changes in adenine, which also had connection with the concentration of IL-17 and the abundance of gamma delta T.