show Abstracthide AbstractAs an essential member of the B7 family, VSIG4 (V-set and immunoglobulin domain-containing 4) is expressed explicitly in tissue-resident macrophages (TRM) of digestive organs and plays an essential role in maintaining the homeostasis of the environmental immune system. Here we demonstrate that gene-targeted VSIG4-deficient mice infected with EHEC (Enterohemorrhagic Escherichia coli) display reduced bacterial burden. To address the functional protection of VSIG4 against EHEC infection. We collected mouse feces and used the High-throughput 16S rRNA gene amplicon analysis to detect. A total of 657330 sequences were sequenced on the PacBio platform, with an average length of 1498bp. We found that VSIG4-deficiency could alter the gut microbiota by increasing diversity and shifting community composition, which G_Akkermansia and G_Oscillospiraceae increased significantly. These findings extend a prior observation that VSIG4-deficiency reduced bacterial burdon by changing the gut microbiota diversity or shifting community composition.