RT Journal Article
SR Electronic
T1 A purified membrane protein from <em>Akkermansia muciniphila</em> or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8<sup>+</sup> T cells in mice
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1988
OP 1997
DO 10.1136/gutjnl-2019-320105
VO 69
IS 11
A1 Lijuan Wang
A1 Lei Tang
A1 Yiming Feng
A1 Suying Zhao
A1 Mei Han
A1 Chuan Zhang
A1 Gehui Yuan
A1 Jun Zhu
A1 Shuyuan Cao
A1 Qian Wu
A1 Lei Li
A1 Zhan Zhang
YR 2020
UL http://gut.bmj.com/content/69/11/1988.abstract
AB 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.