OBJECTIVE

Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). () is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates how engages the immune response in CAC.

DESIGN

Mice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised or a specific outer membrane protein (Amuc_1100) treatment. Faeces from mice and patients with IBD or CRC were collected for 16S rRNA sequencing. The effects of or Amuc_1100 on the immune response in acute colitis and CAC were investigated.

RESULTS

was significantly reduced in patients with IBD and mice with colitis or CAC. or Amuc_1100 could improve colitis, with a reduction in infiltrating macrophages and CD8 cytotoxic T lymphocytes (CTLs) in the colon. Their treatment also decreased CD16/32 macrophages in the spleen and mesenteric lymph nodes (MLN) of colitis mice. Amuc_1100 elevated PD-1 CTLs in the spleen. Moreover, and Amuc_1100 blunted tumourigenesis by expanding CTLs in the colon and MLN. Remarkably, they activated CTLs in the MLN, as indicated by TNF-α induction and PD-1downregulation. Amuc_1100 could stimulate and activate CTLs from splenocytes in CT26 cell conditioned medium.

CONCLUSIONS

These data indicate that pasteurised or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.