Acetyltransferase fromAkkermansia muciniphilablunts colorectal tumourigenesis by reprogramming tumour microenvironment

Abstract

ObjectiveThe protein post-translational modification (PTM) in host cells can be rewritten by bacterial enzymes and represents an unprecedented mechanism in the communication between intestinal flora and the host. AlthoughAkkermansia muciniphilahas been widely investigated as a probiotic and blunts colitis-associated tumourigenesis in mice, there is little understanding regarding whetherA. muciniphilais involved in the PTM of colorectal cancer (CRC). This study investigates whether and howA. muciniphilaengages in the PTM of host CRC.DesignThe secreting extracellular vesicles fromA. muciniphilaand purified Amuc_2172 were used for different tumourigenesis mice models. Amuc_2172-induced immune activity of CD8+cytotoxic T lymphocytes (CTLs) were evaluated in vitro and in vivo. The acetyltransferase activity and downstream target genes of Amuc_2172 were investigated.ResultsAmuc_2172, a general control non-derepressible 5-related acetyltransferase ofA. muciniphila, was accessible to colorectal cells by macropinocytosis and functioned as an acetyltransferase of Lys14 on histone H3 (H3K14ac). Elevated H3K14ac onHspa1aloci promoted the transcription and secretion of heat-shock protein 70 (HSP70) in cancer cells. High level of HSP70 promoted the immune activity of CTLs in vitro and in vivo. Moreover, bioengineered nanoparticles provided a safe and reliable drug delivery strategy of Amuc_2172 for CRC treatment in an allograft mice model.ConclusionAmuc_2172 reprogrammed tumour microenvironment by inducing HSP70 secretion and promoting CTL-related immune response in the process of tumourigenesis.

Distinct intratumoral microbiome of young-onset and average-onset colorectal cancer

“… 70 Additionally, supplementation of Akkermansia mucinophilia suppressed colorectal tumorigenesis in mice models by reprogramming the tumor microenvironment. 71 Similar to these studies, the analysis of ao CRC tumors in our study revealed that Akkermansia was relatively abundant in primary tumors of patients with earlier stages of the disease as compared to metastatic disease, and Akkermansia abundance negatively correlated with tumor size.…”

Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001–2023)

“…Many species have exhibited therapeutic potential ( Chiva et al, 2002 ; Liu et al, 2020 ). A. muciniphila is a rising probiotic in recent years and has gained wide acknowledgement in different diseases such as obesity ( Depommier et al, 2019 ), colorectal cancer ( Jiang et al, 2023 ) and liver diseases ( Rao et al, 2021 ). Present findings indicate its therapeutic role in early stage in including NAFLD ( Depommier et al, 2019 ; Rao et al, 2021 ) and ALD ( Grander et al, 2020 ), whilst its role in advanced liver cirrhosis has not been detected.…”

New sights of immunometabolism and agent progress in colitis associated colorectal cancer

“…This activation leads to the promotion of tumour invasion and resistance to chemotherapy ( Yang et al, 2020 ). Tumor cells alter their metabolic pathways, such as increasing glycolysis and fatty acid oxidation while suppressing oxidative phosphorylation, in order to fulfil their bioenergy requirements associated with EMT ( Jiang et al, 2023 ).…”