Akkermansia muciniphila administration exacerbated the development of colitis-associated colorectal cancer in mice

Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein Amuc_1434 (expressed in Escherichia coli prokaryote cell system, hereinafter termed Amuc_1434*), derived from Akkermansia muciniphila, can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived from Akkermansia muciniphila suppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.

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Relationship of the mucin-degrading bacterium Akkermansia muciniphila with colorectal cancer

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-178-6-158-165 ◽

2020 ◽

pp. 158-165

Author(s):

A. M. Karamzin ◽

A. V. Ropot ◽

R. E. Boshian

Keyword(s):

Colorectal Cancer ◽

Intestinal Microbiota ◽

Cancer Development ◽

Akkermansia Muciniphila ◽

Degrading Bacterium ◽

The World ◽

Cast Doubt ◽

The Russian Federation ◽

Relationship Of ◽

The Relationship

Colorectal cancer is a disease that is far from the last place in the morbidity statistics in the Russian Federation and in the world. Along with well-known risk factors for the development of this pathology, some representatives of the intestinal microbiota are possible to participate in this process. Some studies suggest that Akkermansia muciniphila, a mucin-degrading bacterium, is associated with colorectal cancer development, but other studies cast doubt on this statement. In this review, we describe a series of studies devoted to determining the dependence of colorectal cancer on the amount of A. muciniphila, the relationship of this bacterium with inflammation development as a predictor of oncogenesis, the influence of other representatives of the intestinal microbiota on its function, and also describe one of the possible mechanisms linking the mucin-degraging ability of this bacterium with the development of oncogenesis.

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

Gut ◽

10.1136/gutjnl-2019-320105 ◽

2020 ◽

Vol 69 (11) ◽

pp. 1988-1997 ◽

Cited By ~ 8

Author(s):

Lijuan Wang ◽

Lei Tang ◽

Yiming Feng ◽

Suying Zhao ◽

Mei Han ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Response ◽

Membrane Protein ◽

Causative Role ◽

Mesenteric Lymph Nodes ◽

Akkermansia Muciniphila ◽

Tnf Α ◽

Rrna Sequencing ◽

Inflammatory Bowel ◽

Cell Conditioned Medium

ObjectiveGut 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.DesignMice 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.ResultsA. 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.ConclusionsThese data indicate that pasteurised A. muciniphila or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.

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Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-82465-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Muhammad Afiq Osman ◽

Hui-min Neoh ◽

Nurul-Syakima Ab Mutalib ◽

Siok-Fong Chin ◽

Luqman Mazlan ◽

...

Keyword(s):

Colorectal Cancer ◽

Validation Cohort ◽

Small Sample Size ◽

Fusobacterium Nucleatum ◽

Small Sample ◽

Kuala Lumpur ◽

Akkermansia Muciniphila ◽

Mucosal Tissues ◽

Parvimonas Micra ◽

Species Specific

AbstractDysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

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