Akkermansia muciniphila

Biology

Colorectal cancer

Inflammatory bowel disease

Azoxymethane

Biochemistry

Immunology

Immune system

Colitis

In vitro

Microbiology

Internal medicine

Cytotoxic T cell

Gut flora

Medicine

Ulcerative colitis

Disease

Cancer

Objective Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). Akkermansia muciniphila ( A. muciniphila ) 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 A. muciniphila 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 A. muciniphila 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 A. muciniphila or Amuc_1100 on the immune response in acute colitis and CAC were investigated. Results A. muciniphila was significantly reduced in patients with IBD and mice with colitis or CAC. A. muciniphila 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, A. muciniphila 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 A. muciniphila or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.

A purified membrane protein from <i>Akkermansia muciniphila</i> or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8<sup>+</sup> T cells in mice

A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice

A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8⁺ T cells in mice