A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice
Authors: Mei Han
Jun Zhu
Shuyuan Cao
Lijuan Wang
Qian Wu
Zhan Zhang
Gehui Yuan
Yiming Feng
Lei Li
Lei Tang
Chuan Zhang
Suying Zhao
Journal: Gut (2020)
Discipline: CLINICAL MEDICINE
Keywords: colonic microflora; colorectal cancer; experimental colitis; gut immunology; nutritional supplementation.
Affiliations: Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China., Department of laboratory medicine, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China., Department of General Surgery, Jiangsu Province People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China., Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China  .

Abstract:  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. 

Retracted: No

PubPeer comments:
 The paper duplicates a SEM micrograph previously published by Jo et al. 2007 (see image below). The micrograph, which originally represented nano-SiO2, was manipulated in terms of orientation, scale, aspect ratio, brightness, and contrast, and claimed to represent nano-Fe2O3. Appropriate credit was not given to the original source. ![file] , 
 The paper reportedly used cement that was chemically and physically identical to that previously used by the group of Alireza Najigivi (see image below). This claim seems highly implausible, since the Najigivi group was working in Malaysia and the Nazari group was working in Iran. In a corrigendum by the Nazari group in a related work, it was stated that the work was originally performed by the Najigivi group. The source was not appropriately cited. ![file] ,