LAUSR

The host microbiota is tightly associated with tumor initiation and progression in multiple solid tumors including gastric cancer (GC). The aim of this study was to investigate in patients with GC whether there are alterations in gastric microbiota and any potential association these may have with immune dysregulation. 16S rRNA gene sequencing was used to analyze tumor microbiota of 53 patients with GC and gastric mucosal tissue microbiota of 30 patients with chronic gastritis. The effect of microbiota on the tumor microenvironment (TME) was studied by single-cell sequencing, immunohistochemistry, multiplex immunofluorescence staining, and flow cytometry, as well as in a mouse model of primary GC. The GC microbiota was characterized by reduced microbial diversity and enrichment of the Oceanobacter, Methylobacterium and Syntrophomonas genera. Intratumoral Methylobacterium was significantly associated with poor prognoses in GC patients. It also was inversely correlated with the frequency of CD8+ tissue-resident memory T (TRM) cells in the TME. TGFβ was significantly reduced in GC samples with higher abundance of Methylobacterium. Finally, we verified that Methylobacterium can decrease TGFβ expression and CD8+ TRM cells in the tumor by establishing a mouse model of primary GC. The results suggest that tumor microbiota and exhausted CD8+ TRM cells in the TME of GC are significantly correlated, and that Methylobacterium may play a role in gastric carcinogenesis.